ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4675G>C (p.Glu1559Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4675G>C (p.Glu1559Gln)
Variation ID: 37605 Accession: VCV000037605.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074331 (GRCh38) [ NCBI UCSC ] 17: 41226348 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 May 1, 2024 May 2, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.4675G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1559Gln missense NM_001407571.1:c.4462G>C NP_001394500.1:p.Glu1488Gln missense NM_001407581.1:c.4741G>C NP_001394510.1:p.Glu1581Gln missense NM_001407582.1:c.4741G>C NP_001394511.1:p.Glu1581Gln missense NM_001407583.1:c.4738G>C NP_001394512.1:p.Glu1580Gln missense NM_001407585.1:c.4738G>C NP_001394514.1:p.Glu1580Gln missense NM_001407587.1:c.4738G>C NP_001394516.1:p.Glu1580Gln missense NM_001407590.1:c.4735G>C NP_001394519.1:p.Glu1579Gln missense NM_001407591.1:c.4735G>C NP_001394520.1:p.Glu1579Gln missense NM_001407593.1:c.4675G>C NP_001394522.1:p.Glu1559Gln missense NM_001407594.1:c.4675G>C NP_001394523.1:p.Glu1559Gln missense NM_001407596.1:c.4675G>C NP_001394525.1:p.Glu1559Gln missense NM_001407597.1:c.4675G>C NP_001394526.1:p.Glu1559Gln missense NM_001407598.1:c.4675G>C NP_001394527.1:p.Glu1559Gln missense NM_001407602.1:c.4675G>C NP_001394531.1:p.Glu1559Gln missense NM_001407603.1:c.4675G>C NP_001394532.1:p.Glu1559Gln missense NM_001407605.1:c.4675G>C NP_001394534.1:p.Glu1559Gln missense NM_001407610.1:c.4672G>C NP_001394539.1:p.Glu1558Gln missense NM_001407611.1:c.4672G>C NP_001394540.1:p.Glu1558Gln missense NM_001407612.1:c.4672G>C NP_001394541.1:p.Glu1558Gln missense NM_001407613.1:c.4672G>C NP_001394542.1:p.Glu1558Gln missense NM_001407614.1:c.4672G>C NP_001394543.1:p.Glu1558Gln missense NM_001407615.1:c.4672G>C NP_001394544.1:p.Glu1558Gln missense NM_001407616.1:c.4672G>C NP_001394545.1:p.Glu1558Gln missense NM_001407617.1:c.4672G>C NP_001394546.1:p.Glu1558Gln missense NM_001407618.1:c.4672G>C NP_001394547.1:p.Glu1558Gln missense NM_001407619.1:c.4672G>C NP_001394548.1:p.Glu1558Gln missense NM_001407620.1:c.4672G>C NP_001394549.1:p.Glu1558Gln missense NM_001407621.1:c.4672G>C NP_001394550.1:p.Glu1558Gln missense NM_001407622.1:c.4672G>C NP_001394551.1:p.Glu1558Gln missense NM_001407623.1:c.4672G>C NP_001394552.1:p.Glu1558Gln missense NM_001407624.1:c.4672G>C NP_001394553.1:p.Glu1558Gln missense NM_001407625.1:c.4672G>C NP_001394554.1:p.Glu1558Gln missense NM_001407626.1:c.4672G>C NP_001394555.1:p.Glu1558Gln missense NM_001407627.1:c.4669G>C NP_001394556.1:p.Glu1557Gln missense NM_001407628.1:c.4669G>C NP_001394557.1:p.Glu1557Gln missense NM_001407629.1:c.4669G>C NP_001394558.1:p.Glu1557Gln missense NM_001407630.1:c.4669G>C NP_001394559.1:p.Glu1557Gln missense NM_001407631.1:c.4669G>C NP_001394560.1:p.Glu1557Gln missense NM_001407632.1:c.4669G>C NP_001394561.1:p.Glu1557Gln missense NM_001407633.1:c.4669G>C NP_001394562.1:p.Glu1557Gln missense NM_001407634.1:c.4669G>C NP_001394563.1:p.Glu1557Gln missense NM_001407635.1:c.4669G>C NP_001394564.1:p.Glu1557Gln missense NM_001407636.1:c.4669G>C NP_001394565.1:p.Glu1557Gln missense NM_001407637.1:c.4669G>C NP_001394566.1:p.Glu1557Gln missense NM_001407638.1:c.4669G>C NP_001394567.1:p.Glu1557Gln missense NM_001407639.1:c.4669G>C NP_001394568.1:p.Glu1557Gln missense NM_001407640.1:c.4669G>C NP_001394569.1:p.Glu1557Gln missense NM_001407641.1:c.4669G>C NP_001394570.1:p.Glu1557Gln missense NM_001407642.1:c.4669G>C NP_001394571.1:p.Glu1557Gln missense NM_001407644.1:c.4666G>C NP_001394573.1:p.Glu1556Gln missense NM_001407645.1:c.4666G>C NP_001394574.1:p.Glu1556Gln missense NM_001407646.1:c.4663G>C NP_001394575.1:p.Glu1555Gln missense NM_001407647.1:c.4660G>C NP_001394576.1:p.Glu1554Gln missense NM_001407648.1:c.4618G>C NP_001394577.1:p.Glu1540Gln missense NM_001407649.1:c.4615G>C NP_001394578.1:p.Glu1539Gln missense NM_001407652.1:c.4675G>C NP_001394581.1:p.Glu1559Gln missense NM_001407653.1:c.4597G>C NP_001394582.1:p.Glu1533Gln missense NM_001407654.1:c.4597G>C NP_001394583.1:p.Glu1533Gln missense NM_001407655.1:c.4597G>C NP_001394584.1:p.Glu1533Gln missense NM_001407656.1:c.4594G>C NP_001394585.1:p.Glu1532Gln missense NM_001407657.1:c.4594G>C NP_001394586.1:p.Glu1532Gln missense NM_001407658.1:c.4594G>C NP_001394587.1:p.Glu1532Gln missense NM_001407659.1:c.4591G>C NP_001394588.1:p.Glu1531Gln missense NM_001407660.1:c.4591G>C NP_001394589.1:p.Glu1531Gln missense NM_001407661.1:c.4591G>C NP_001394590.1:p.Glu1531Gln missense NM_001407662.1:c.4591G>C NP_001394591.1:p.Glu1531Gln missense NM_001407663.1:c.4591G>C NP_001394592.1:p.Glu1531Gln missense NM_001407664.1:c.4552G>C NP_001394593.1:p.Glu1518Gln missense NM_001407665.1:c.4552G>C NP_001394594.1:p.Glu1518Gln missense NM_001407666.1:c.4552G>C NP_001394595.1:p.Glu1518Gln missense NM_001407667.1:c.4552G>C NP_001394596.1:p.Glu1518Gln missense NM_001407668.1:c.4552G>C NP_001394597.1:p.Glu1518Gln missense NM_001407669.1:c.4552G>C NP_001394598.1:p.Glu1518Gln missense NM_001407670.1:c.4549G>C NP_001394599.1:p.Glu1517Gln missense NM_001407671.1:c.4549G>C NP_001394600.1:p.Glu1517Gln missense NM_001407672.1:c.4549G>C NP_001394601.1:p.Glu1517Gln missense NM_001407673.1:c.4549G>C NP_001394602.1:p.Glu1517Gln missense NM_001407674.1:c.4549G>C NP_001394603.1:p.Glu1517Gln missense NM_001407675.1:c.4549G>C NP_001394604.1:p.Glu1517Gln missense NM_001407676.1:c.4549G>C NP_001394605.1:p.Glu1517Gln missense NM_001407677.1:c.4549G>C NP_001394606.1:p.Glu1517Gln missense NM_001407678.1:c.4549G>C NP_001394607.1:p.Glu1517Gln missense NM_001407679.1:c.4549G>C NP_001394608.1:p.Glu1517Gln missense NM_001407680.1:c.4549G>C NP_001394609.1:p.Glu1517Gln missense NM_001407681.1:c.4546G>C NP_001394610.1:p.Glu1516Gln missense NM_001407682.1:c.4546G>C NP_001394611.1:p.Glu1516Gln missense NM_001407683.1:c.4546G>C NP_001394612.1:p.Glu1516Gln missense NM_001407684.1:c.4675G>C NP_001394613.1:p.Glu1559Gln missense NM_001407685.1:c.4546G>C NP_001394614.1:p.Glu1516Gln missense NM_001407686.1:c.4546G>C NP_001394615.1:p.Glu1516Gln missense NM_001407687.1:c.4546G>C NP_001394616.1:p.Glu1516Gln missense NM_001407688.1:c.4546G>C NP_001394617.1:p.Glu1516Gln missense NM_001407689.1:c.4546G>C NP_001394618.1:p.Glu1516Gln missense NM_001407690.1:c.4543G>C NP_001394619.1:p.Glu1515Gln missense NM_001407691.1:c.4543G>C NP_001394620.1:p.Glu1515Gln missense NM_001407692.1:c.4534G>C NP_001394621.1:p.Glu1512Gln missense NM_001407694.1:c.4534G>C NP_001394623.1:p.Glu1512Gln missense NM_001407695.1:c.4534G>C NP_001394624.1:p.Glu1512Gln missense NM_001407696.1:c.4534G>C NP_001394625.1:p.Glu1512Gln missense NM_001407697.1:c.4534G>C NP_001394626.1:p.Glu1512Gln missense NM_001407698.1:c.4534G>C NP_001394627.1:p.Glu1512Gln missense NM_001407724.1:c.4534G>C NP_001394653.1:p.Glu1512Gln missense NM_001407725.1:c.4534G>C NP_001394654.1:p.Glu1512Gln missense NM_001407726.1:c.4534G>C NP_001394655.1:p.Glu1512Gln missense NM_001407727.1:c.4534G>C NP_001394656.1:p.Glu1512Gln missense NM_001407728.1:c.4534G>C NP_001394657.1:p.Glu1512Gln missense NM_001407729.1:c.4534G>C NP_001394658.1:p.Glu1512Gln missense NM_001407730.1:c.4534G>C NP_001394659.1:p.Glu1512Gln missense NM_001407731.1:c.4534G>C NP_001394660.1:p.Glu1512Gln missense NM_001407732.1:c.4531G>C NP_001394661.1:p.Glu1511Gln missense NM_001407733.1:c.4531G>C NP_001394662.1:p.Glu1511Gln missense NM_001407734.1:c.4531G>C NP_001394663.1:p.Glu1511Gln missense NM_001407735.1:c.4531G>C NP_001394664.1:p.Glu1511Gln missense NM_001407736.1:c.4531G>C NP_001394665.1:p.Glu1511Gln missense NM_001407737.1:c.4531G>C NP_001394666.1:p.Glu1511Gln missense NM_001407738.1:c.4531G>C NP_001394667.1:p.Glu1511Gln missense NM_001407739.1:c.4531G>C NP_001394668.1:p.Glu1511Gln missense NM_001407740.1:c.4531G>C NP_001394669.1:p.Glu1511Gln missense NM_001407741.1:c.4531G>C NP_001394670.1:p.Glu1511Gln missense NM_001407742.1:c.4531G>C NP_001394671.1:p.Glu1511Gln missense NM_001407743.1:c.4531G>C NP_001394672.1:p.Glu1511Gln missense NM_001407744.1:c.4531G>C NP_001394673.1:p.Glu1511Gln missense NM_001407745.1:c.4531G>C NP_001394674.1:p.Glu1511Gln missense NM_001407746.1:c.4531G>C NP_001394675.1:p.Glu1511Gln missense NM_001407747.1:c.4531G>C NP_001394676.1:p.Glu1511Gln missense NM_001407748.1:c.4531G>C NP_001394677.1:p.Glu1511Gln missense NM_001407749.1:c.4531G>C NP_001394678.1:p.Glu1511Gln missense NM_001407750.1:c.4531G>C NP_001394679.1:p.Glu1511Gln missense NM_001407751.1:c.4531G>C NP_001394680.1:p.Glu1511Gln missense NM_001407752.1:c.4531G>C NP_001394681.1:p.Glu1511Gln missense NM_001407838.1:c.4528G>C NP_001394767.1:p.Glu1510Gln missense NM_001407839.1:c.4528G>C NP_001394768.1:p.Glu1510Gln missense NM_001407841.1:c.4528G>C NP_001394770.1:p.Glu1510Gln missense NM_001407842.1:c.4528G>C NP_001394771.1:p.Glu1510Gln missense NM_001407843.1:c.4528G>C NP_001394772.1:p.Glu1510Gln missense NM_001407844.1:c.4528G>C NP_001394773.1:p.Glu1510Gln missense NM_001407845.1:c.4528G>C NP_001394774.1:p.Glu1510Gln missense NM_001407846.1:c.4528G>C NP_001394775.1:p.Glu1510Gln missense NM_001407847.1:c.4528G>C NP_001394776.1:p.Glu1510Gln missense NM_001407848.1:c.4528G>C NP_001394777.1:p.Glu1510Gln missense NM_001407849.1:c.4528G>C NP_001394778.1:p.Glu1510Gln missense NM_001407850.1:c.4528G>C NP_001394779.1:p.Glu1510Gln missense NM_001407851.1:c.4528G>C NP_001394780.1:p.Glu1510Gln missense NM_001407852.1:c.4528G>C NP_001394781.1:p.Glu1510Gln missense NM_001407853.1:c.4528G>C NP_001394782.1:p.Glu1510Gln missense NM_001407854.1:c.4675G>C NP_001394783.1:p.Glu1559Gln missense NM_001407858.1:c.4672G>C NP_001394787.1:p.Glu1558Gln missense NM_001407859.1:c.4672G>C NP_001394788.1:p.Glu1558Gln missense NM_001407860.1:c.4672G>C NP_001394789.1:p.Glu1558Gln missense NM_001407861.1:c.4669G>C NP_001394790.1:p.Glu1557Gln missense NM_001407862.1:c.4474G>C NP_001394791.1:p.Glu1492Gln missense NM_001407863.1:c.4549G>C NP_001394792.1:p.Glu1517Gln missense NM_001407874.1:c.4468G>C NP_001394803.1:p.Glu1490Gln missense NM_001407875.1:c.4468G>C NP_001394804.1:p.Glu1490Gln missense NM_001407879.1:c.4465G>C NP_001394808.1:p.Glu1489Gln missense NM_001407881.1:c.4465G>C NP_001394810.1:p.Glu1489Gln missense NM_001407882.1:c.4465G>C NP_001394811.1:p.Glu1489Gln missense NM_001407884.1:c.4465G>C NP_001394813.1:p.Glu1489Gln missense NM_001407885.1:c.4465G>C NP_001394814.1:p.Glu1489Gln missense NM_001407886.1:c.4465G>C NP_001394815.1:p.Glu1489Gln missense NM_001407887.1:c.4465G>C NP_001394816.1:p.Glu1489Gln missense NM_001407889.1:c.4465G>C NP_001394818.1:p.Glu1489Gln missense NM_001407894.1:c.4462G>C NP_001394823.1:p.Glu1488Gln missense NM_001407895.1:c.4462G>C NP_001394824.1:p.Glu1488Gln missense NM_001407896.1:c.4462G>C NP_001394825.1:p.Glu1488Gln missense NM_001407897.1:c.4462G>C NP_001394826.1:p.Glu1488Gln missense NM_001407898.1:c.4462G>C NP_001394827.1:p.Glu1488Gln missense NM_001407899.1:c.4462G>C NP_001394828.1:p.Glu1488Gln missense NM_001407900.1:c.4462G>C NP_001394829.1:p.Glu1488Gln missense NM_001407902.1:c.4462G>C NP_001394831.1:p.Glu1488Gln missense NM_001407904.1:c.4462G>C NP_001394833.1:p.Glu1488Gln missense NM_001407906.1:c.4462G>C NP_001394835.1:p.Glu1488Gln missense NM_001407907.1:c.4462G>C NP_001394836.1:p.Glu1488Gln missense NM_001407908.1:c.4462G>C NP_001394837.1:p.Glu1488Gln missense NM_001407909.1:c.4462G>C NP_001394838.1:p.Glu1488Gln missense NM_001407910.1:c.4462G>C NP_001394839.1:p.Glu1488Gln missense NM_001407915.1:c.4459G>C NP_001394844.1:p.Glu1487Gln missense NM_001407916.1:c.4459G>C NP_001394845.1:p.Glu1487Gln missense NM_001407917.1:c.4459G>C NP_001394846.1:p.Glu1487Gln missense NM_001407918.1:c.4459G>C NP_001394847.1:p.Glu1487Gln missense NM_001407919.1:c.4552G>C NP_001394848.1:p.Glu1518Gln missense NM_001407920.1:c.4411G>C NP_001394849.1:p.Glu1471Gln missense NM_001407921.1:c.4411G>C NP_001394850.1:p.Glu1471Gln missense NM_001407922.1:c.4411G>C NP_001394851.1:p.Glu1471Gln missense NM_001407923.1:c.4411G>C NP_001394852.1:p.Glu1471Gln missense NM_001407924.1:c.4411G>C NP_001394853.1:p.Glu1471Gln missense NM_001407925.1:c.4411G>C NP_001394854.1:p.Glu1471Gln missense NM_001407926.1:c.4411G>C NP_001394855.1:p.Glu1471Gln missense NM_001407927.1:c.4408G>C NP_001394856.1:p.Glu1470Gln missense NM_001407928.1:c.4408G>C NP_001394857.1:p.Glu1470Gln missense NM_001407929.1:c.4408G>C NP_001394858.1:p.Glu1470Gln missense NM_001407930.1:c.4408G>C NP_001394859.1:p.Glu1470Gln missense NM_001407931.1:c.4408G>C NP_001394860.1:p.Glu1470Gln missense NM_001407932.1:c.4408G>C NP_001394861.1:p.Glu1470Gln missense NM_001407933.1:c.4408G>C NP_001394862.1:p.Glu1470Gln missense NM_001407934.1:c.4405G>C NP_001394863.1:p.Glu1469Gln missense NM_001407935.1:c.4405G>C NP_001394864.1:p.Glu1469Gln missense NM_001407936.1:c.4405G>C NP_001394865.1:p.Glu1469Gln missense NM_001407937.1:c.4552G>C NP_001394866.1:p.Glu1518Gln missense NM_001407938.1:c.4552G>C NP_001394867.1:p.Glu1518Gln missense NM_001407939.1:c.4549G>C NP_001394868.1:p.Glu1517Gln missense NM_001407940.1:c.4549G>C NP_001394869.1:p.Glu1517Gln missense NM_001407941.1:c.4546G>C NP_001394870.1:p.Glu1516Gln missense NM_001407942.1:c.4534G>C NP_001394871.1:p.Glu1512Gln missense NM_001407943.1:c.4531G>C NP_001394872.1:p.Glu1511Gln missense NM_001407944.1:c.4531G>C NP_001394873.1:p.Glu1511Gln missense NM_001407945.1:c.4531G>C NP_001394874.1:p.Glu1511Gln missense NM_001407946.1:c.4342G>C NP_001394875.1:p.Glu1448Gln missense NM_001407947.1:c.4342G>C NP_001394876.1:p.Glu1448Gln missense NM_001407948.1:c.4342G>C NP_001394877.1:p.Glu1448Gln missense NM_001407949.1:c.4342G>C NP_001394878.1:p.Glu1448Gln missense NM_001407950.1:c.4339G>C NP_001394879.1:p.Glu1447Gln missense NM_001407951.1:c.4339G>C NP_001394880.1:p.Glu1447Gln missense NM_001407952.1:c.4339G>C NP_001394881.1:p.Glu1447Gln missense NM_001407953.1:c.4339G>C NP_001394882.1:p.Glu1447Gln missense NM_001407954.1:c.4339G>C NP_001394883.1:p.Glu1447Gln missense NM_001407955.1:c.4339G>C NP_001394884.1:p.Glu1447Gln missense NM_001407956.1:c.4336G>C NP_001394885.1:p.Glu1446Gln missense NM_001407957.1:c.4336G>C NP_001394886.1:p.Glu1446Gln missense NM_001407958.1:c.4336G>C NP_001394887.1:p.Glu1446Gln missense NM_001407959.1:c.4294G>C NP_001394888.1:p.Glu1432Gln missense NM_001407960.1:c.4291G>C NP_001394889.1:p.Glu1431Gln missense NM_001407962.1:c.4291G>C NP_001394891.1:p.Glu1431Gln missense NM_001407963.1:c.4288G>C NP_001394892.1:p.Glu1430Gln missense NM_001407965.1:c.4168G>C NP_001394894.1:p.Glu1390Gln missense NM_001407966.1:c.3787G>C NP_001394895.1:p.Glu1263Gln missense NM_001407967.1:c.3784G>C NP_001394896.1:p.Glu1262Gln missense NM_001407968.1:c.2071G>C NP_001394897.1:p.Glu691Gln missense NM_001407969.1:c.2068G>C NP_001394898.1:p.Glu690Gln missense NM_001407970.1:c.1432G>C NP_001394899.1:p.Glu478Gln missense NM_001407971.1:c.1432G>C NP_001394900.1:p.Glu478Gln missense NM_001407972.1:c.1429G>C NP_001394901.1:p.Glu477Gln missense NM_001407973.1:c.1366G>C NP_001394902.1:p.Glu456Gln missense NM_001407974.1:c.1366G>C NP_001394903.1:p.Glu456Gln missense NM_001407975.1:c.1366G>C NP_001394904.1:p.Glu456Gln missense NM_001407976.1:c.1366G>C NP_001394905.1:p.Glu456Gln missense NM_001407977.1:c.1366G>C NP_001394906.1:p.Glu456Gln missense NM_001407978.1:c.1366G>C NP_001394907.1:p.Glu456Gln missense NM_001407979.1:c.1363G>C NP_001394908.1:p.Glu455Gln missense NM_001407980.1:c.1363G>C NP_001394909.1:p.Glu455Gln missense NM_001407981.1:c.1363G>C NP_001394910.1:p.Glu455Gln missense NM_001407982.1:c.1363G>C NP_001394911.1:p.Glu455Gln missense NM_001407983.1:c.1363G>C NP_001394912.1:p.Glu455Gln missense NM_001407984.1:c.1363G>C NP_001394913.1:p.Glu455Gln missense NM_001407985.1:c.1363G>C NP_001394914.1:p.Glu455Gln missense NM_001407986.1:c.1363G>C NP_001394915.1:p.Glu455Gln missense NM_001407990.1:c.1363G>C NP_001394919.1:p.Glu455Gln missense NM_001407991.1:c.1363G>C NP_001394920.1:p.Glu455Gln missense NM_001407992.1:c.1363G>C NP_001394921.1:p.Glu455Gln missense NM_001407993.1:c.1363G>C NP_001394922.1:p.Glu455Gln missense NM_001408392.1:c.1360G>C NP_001395321.1:p.Glu454Gln missense NM_001408396.1:c.1360G>C NP_001395325.1:p.Glu454Gln missense NM_001408397.1:c.1360G>C NP_001395326.1:p.Glu454Gln missense NM_001408398.1:c.1360G>C NP_001395327.1:p.Glu454Gln missense NM_001408399.1:c.1360G>C NP_001395328.1:p.Glu454Gln missense NM_001408400.1:c.1360G>C NP_001395329.1:p.Glu454Gln missense NM_001408401.1:c.1360G>C NP_001395330.1:p.Glu454Gln missense NM_001408402.1:c.1360G>C NP_001395331.1:p.Glu454Gln missense NM_001408403.1:c.1360G>C NP_001395332.1:p.Glu454Gln missense NM_001408404.1:c.1360G>C NP_001395333.1:p.Glu454Gln missense NM_001408406.1:c.1357G>C NP_001395335.1:p.Glu453Gln missense NM_001408407.1:c.1357G>C NP_001395336.1:p.Glu453Gln missense NM_001408408.1:c.1357G>C NP_001395337.1:p.Glu453Gln missense NM_001408409.1:c.1354G>C NP_001395338.1:p.Glu452Gln missense NM_001408410.1:c.1291G>C NP_001395339.1:p.Glu431Gln missense NM_001408411.1:c.1288G>C NP_001395340.1:p.Glu430Gln missense NM_001408412.1:c.1285G>C NP_001395341.1:p.Glu429Gln missense NM_001408413.1:c.1285G>C NP_001395342.1:p.Glu429Gln missense NM_001408414.1:c.1285G>C NP_001395343.1:p.Glu429Gln missense NM_001408415.1:c.1285G>C NP_001395344.1:p.Glu429Gln missense NM_001408416.1:c.1285G>C NP_001395345.1:p.Glu429Gln missense NM_001408418.1:c.1249G>C NP_001395347.1:p.Glu417Gln missense NM_001408419.1:c.1249G>C NP_001395348.1:p.Glu417Gln missense NM_001408420.1:c.1249G>C NP_001395349.1:p.Glu417Gln missense NM_001408421.1:c.1246G>C NP_001395350.1:p.Glu416Gln missense NM_001408422.1:c.1246G>C NP_001395351.1:p.Glu416Gln missense NM_001408423.1:c.1246G>C NP_001395352.1:p.Glu416Gln missense NM_001408424.1:c.1246G>C NP_001395353.1:p.Glu416Gln missense NM_001408425.1:c.1243G>C NP_001395354.1:p.Glu415Gln missense NM_001408426.1:c.1243G>C NP_001395355.1:p.Glu415Gln missense NM_001408427.1:c.1243G>C NP_001395356.1:p.Glu415Gln missense NM_001408428.1:c.1243G>C NP_001395357.1:p.Glu415Gln missense NM_001408429.1:c.1243G>C NP_001395358.1:p.Glu415Gln missense NM_001408430.1:c.1243G>C NP_001395359.1:p.Glu415Gln missense NM_001408431.1:c.1243G>C NP_001395360.1:p.Glu415Gln missense NM_001408432.1:c.1240G>C NP_001395361.1:p.Glu414Gln missense NM_001408433.1:c.1240G>C NP_001395362.1:p.Glu414Gln missense NM_001408434.1:c.1240G>C NP_001395363.1:p.Glu414Gln missense NM_001408435.1:c.1240G>C NP_001395364.1:p.Glu414Gln missense NM_001408436.1:c.1240G>C NP_001395365.1:p.Glu414Gln missense NM_001408437.1:c.1240G>C NP_001395366.1:p.Glu414Gln missense NM_001408438.1:c.1240G>C NP_001395367.1:p.Glu414Gln missense NM_001408439.1:c.1240G>C NP_001395368.1:p.Glu414Gln missense NM_001408440.1:c.1240G>C NP_001395369.1:p.Glu414Gln missense NM_001408441.1:c.1240G>C NP_001395370.1:p.Glu414Gln missense NM_001408442.1:c.1240G>C NP_001395371.1:p.Glu414Gln missense NM_001408443.1:c.1240G>C NP_001395372.1:p.Glu414Gln missense NM_001408444.1:c.1240G>C NP_001395373.1:p.Glu414Gln missense NM_001408445.1:c.1237G>C NP_001395374.1:p.Glu413Gln missense NM_001408446.1:c.1237G>C NP_001395375.1:p.Glu413Gln missense NM_001408447.1:c.1237G>C NP_001395376.1:p.Glu413Gln missense NM_001408448.1:c.1237G>C NP_001395377.1:p.Glu413Gln missense NM_001408450.1:c.1237G>C NP_001395379.1:p.Glu413Gln missense NM_001408451.1:c.1231G>C NP_001395380.1:p.Glu411Gln missense NM_001408452.1:c.1225G>C NP_001395381.1:p.Glu409Gln missense NM_001408453.1:c.1225G>C NP_001395382.1:p.Glu409Gln missense NM_001408454.1:c.1225G>C NP_001395383.1:p.Glu409Gln missense NM_001408455.1:c.1225G>C NP_001395384.1:p.Glu409Gln missense NM_001408456.1:c.1225G>C NP_001395385.1:p.Glu409Gln missense NM_001408457.1:c.1225G>C NP_001395386.1:p.Glu409Gln missense NM_001408458.1:c.1222G>C NP_001395387.1:p.Glu408Gln missense NM_001408459.1:c.1222G>C NP_001395388.1:p.Glu408Gln missense NM_001408460.1:c.1222G>C NP_001395389.1:p.Glu408Gln missense NM_001408461.1:c.1222G>C NP_001395390.1:p.Glu408Gln missense NM_001408462.1:c.1222G>C NP_001395391.1:p.Glu408Gln missense NM_001408463.1:c.1222G>C NP_001395392.1:p.Glu408Gln missense NM_001408464.1:c.1222G>C NP_001395393.1:p.Glu408Gln missense NM_001408465.1:c.1222G>C NP_001395394.1:p.Glu408Gln missense NM_001408466.1:c.1222G>C NP_001395395.1:p.Glu408Gln missense NM_001408467.1:c.1222G>C NP_001395396.1:p.Glu408Gln missense NM_001408468.1:c.1219G>C NP_001395397.1:p.Glu407Gln missense NM_001408469.1:c.1219G>C NP_001395398.1:p.Glu407Gln missense NM_001408470.1:c.1219G>C NP_001395399.1:p.Glu407Gln missense NM_001408472.1:c.1363G>C NP_001395401.1:p.Glu455Gln missense NM_001408473.1:c.1360G>C NP_001395402.1:p.Glu454Gln missense NM_001408474.1:c.1165G>C NP_001395403.1:p.Glu389Gln missense NM_001408475.1:c.1162G>C NP_001395404.1:p.Glu388Gln missense NM_001408476.1:c.1162G>C NP_001395405.1:p.Glu388Gln missense NM_001408478.1:c.1156G>C NP_001395407.1:p.Glu386Gln missense NM_001408479.1:c.1156G>C NP_001395408.1:p.Glu386Gln missense NM_001408480.1:c.1156G>C NP_001395409.1:p.Glu386Gln missense NM_001408481.1:c.1153G>C NP_001395410.1:p.Glu385Gln missense NM_001408482.1:c.1153G>C NP_001395411.1:p.Glu385Gln missense NM_001408483.1:c.1153G>C NP_001395412.1:p.Glu385Gln missense NM_001408484.1:c.1153G>C NP_001395413.1:p.Glu385Gln missense NM_001408485.1:c.1153G>C NP_001395414.1:p.Glu385Gln missense NM_001408489.1:c.1153G>C NP_001395418.1:p.Glu385Gln missense NM_001408490.1:c.1153G>C NP_001395419.1:p.Glu385Gln missense NM_001408491.1:c.1153G>C NP_001395420.1:p.Glu385Gln missense NM_001408492.1:c.1150G>C NP_001395421.1:p.Glu384Gln missense NM_001408493.1:c.1150G>C NP_001395422.1:p.Glu384Gln missense NM_001408494.1:c.1126G>C NP_001395423.1:p.Glu376Gln missense NM_001408495.1:c.1120G>C NP_001395424.1:p.Glu374Gln missense NM_001408496.1:c.1102G>C NP_001395425.1:p.Glu368Gln missense NM_001408497.1:c.1102G>C NP_001395426.1:p.Glu368Gln missense NM_001408498.1:c.1102G>C NP_001395427.1:p.Glu368Gln missense NM_001408499.1:c.1102G>C NP_001395428.1:p.Glu368Gln missense NM_001408500.1:c.1102G>C NP_001395429.1:p.Glu368Gln missense NM_001408501.1:c.1102G>C NP_001395430.1:p.Glu368Gln missense NM_001408502.1:c.1099G>C NP_001395431.1:p.Glu367Gln missense NM_001408503.1:c.1099G>C NP_001395432.1:p.Glu367Gln missense NM_001408504.1:c.1099G>C NP_001395433.1:p.Glu367Gln missense NM_001408505.1:c.1096G>C NP_001395434.1:p.Glu366Gln missense NM_001408506.1:c.1039G>C NP_001395435.1:p.Glu347Gln missense NM_001408507.1:c.1036G>C NP_001395436.1:p.Glu346Gln missense NM_001408508.1:c.1027G>C NP_001395437.1:p.Glu343Gln missense NM_001408509.1:c.1024G>C NP_001395438.1:p.Glu342Gln missense NM_001408510.1:c.985G>C NP_001395439.1:p.Glu329Gln missense NM_001408511.1:c.982G>C NP_001395440.1:p.Glu328Gln missense NM_001408512.1:c.862G>C NP_001395441.1:p.Glu288Gln missense NM_007297.4:c.4534G>C NP_009228.2:p.Glu1512Gln missense NM_007298.4:c.1363G>C NP_009229.2:p.Glu455Gln missense NM_007299.4:c.1363G>C NP_009230.2:p.Glu455Gln missense NM_007300.3:c.4738G>C NM_007300.4:c.4738G>C NP_009231.2:p.Glu1580Gln missense NM_007304.2:c.1363G>C NP_009235.2:p.Glu455Gln missense NR_027676.2:n.4852G>C non-coding transcript variant NC_000017.11:g.43074331C>G NC_000017.10:g.41226348C>G NG_005905.2:g.143653G>C LRG_292:g.143653G>C LRG_292t1:c.4675G>C LRG_292p1:p.Glu1559Gln U14680.1:n.4794G>C - Protein change
- E1559Q, E455Q, E1580Q, E1512Q, E1447Q, E1516Q, E1554Q, E1556Q, E346Q, E384Q, E388Q, E407Q, E409Q, E413Q, E415Q, E417Q, E453Q, E477Q, E1262Q, E1263Q, E1390Q, E1469Q, E1487Q, E1510Q, E1517Q, E1518Q, E1540Q, E1581Q, E366Q, E367Q, E385Q, E411Q, E454Q, E478Q, E1430Q, E1446Q, E1488Q, E1489Q, E1490Q, E1511Q, E1515Q, E1531Q, E1539Q, E1555Q, E1557Q, E1579Q, E288Q, E342Q, E343Q, E376Q, E386Q, E408Q, E414Q, E416Q, E429Q, E452Q, E456Q, E690Q, E1431Q, E1432Q, E1448Q, E1470Q, E1471Q, E1492Q, E1532Q, E1533Q, E1558Q, E328Q, E329Q, E347Q, E368Q, E374Q, E389Q, E430Q, E431Q, E691Q
- Other names
- 4794G>C
- Canonical SPDI
- NC_000017.11:43074330:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- effect on RNA splicing Variation Ontology [VariO:0362]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13016 | 14818 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Oct 2, 2015 | RCV000031186.23 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 5, 2020 | RCV000131825.17 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
May 2, 2022 | RCV001379224.12 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 24, 2021 | RCV001811228.14 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002050156.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
The BRCA1 c.4675G>C; p.Glu1559Gln variant (rs80356988) is reported in the literature in an individual affected with hereditary breast and ovarian cancer (HBOC) syndrome (Davy 2017). … (more)
The BRCA1 c.4675G>C; p.Glu1559Gln variant (rs80356988) is reported in the literature in an individual affected with hereditary breast and ovarian cancer (HBOC) syndrome (Davy 2017). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant occurs in the last nucleotide of exon 15, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. Consistent with these predictions, mRNA studies demonstrate that the variant leads to aberrant splicing, characterized by skipping of exon 15 or use of a cryptic splice donor 11 nucleotides upstream, both of which lead to frameshifts (Davy 2017). Another variant at the same nucleotide (c.4675G>A) also has been reported in HBOC patients and leads to aberrant splicing (Wangensteen 2019, Wappenschmidt 2012). Based on available information, the c.4675G>C variant is considered to be pathogenic. References: Davy G et al. Detecting splicing patterns in genes involved in hereditary breast and ovarian cancer. Eur J Hum Genet. 2017 Oct;25(10):1147-1154. PMID: 28905878. Wangensteen T et al. Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations. Hered Cancer Clin Pract. 2019 May 22;17:14. PMID: 31143303. Wappenschmidt B et al. Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction. PLoS One. 2012;7(12):e50800. PMID: 23239986. (less)
|
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Likely pathogenic
(May 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001576985.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This variant disrupts the c.4675 nucleotide in the BRCA1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 23239986, 24333842, … (more)
This variant disrupts the c.4675 nucleotide in the BRCA1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 23239986, 24333842, 25066507, 31143303). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. This sequence change affects codon 1559 of the BRCA1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA1 protein. This variant also falls at the last nucleotide of exon 14, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with personal and/or family history of hereditary breast and/or ovarian cancer (PMID: 28975465, 29446198). ClinVar contains an entry for this variant (Variation ID: 37605). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (PMID: 28905878). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Likely pathogenic
(May 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001340175.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 15, 2022 |
Comment:
This missense variant replaces glutamic acid with glutamine at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces glutamic acid with glutamine at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant is located in the last nucleotide of exon 14 of the BRCA1 gene and splice site prediction tools suggest that this variant may impact RNA splicing. An RNA study has shown that this variant causes deletion of the last 11 nucleotides of exon 14 (also know as exon 15 in the literature) and skipping of exon 14 in the RNA transcripts (PMID: 28905878). Both aberrant transcripts are expected to result in an absent or non-functional protein product. This variant has been reported in an individual with personal and/or family history of breast and/or ovarian cancer (PMID: 27157322). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002072886.1
First in ClinVar: Feb 05, 2022 Last updated: Feb 05, 2022 |
Comment:
The missense variant p.E1580Q in BRCA1 (NM_007300.4) has been previously reported as E1559Q in patients affected with breast cancer. Functional studies demonstarted a damaging effect … (more)
The missense variant p.E1580Q in BRCA1 (NM_007300.4) has been previously reported as E1559Q in patients affected with breast cancer. Functional studies demonstarted a damaging effect (Davy G et al,2018). It has been submitted to ClinVar as Pathogenic. The p.E1580Q variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.E1580Q variant is predicted to disrupt splicing by all splice site algorithms. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Multiple cutaneous malignancies (present)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326021.4
First in ClinVar: May 27, 2015 Last updated: Dec 11, 2022 |
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Likely pathogenic
(Jun 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004219416.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in individuals and families with breast and/or ovarian cancer (PMIDs: 29446198 (2018), 28975465 (2017), 27157322 (2016)). … (more)
In the published literature, this variant has been reported in individuals and families with breast and/or ovarian cancer (PMIDs: 29446198 (2018), 28975465 (2017), 27157322 (2016)). Studies assessing BRCA1 mRNA splicing report the variant causes the skipping of exon 14 by deleting the last 11 nucleotides in the exon. This improper splicing is expected to result in frameshifts in the RNA transcripts and an absent or non-functional protein product (PMIDs: 28905878 (2017), 15235020 (2004)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jul 05, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000186880.7
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.4675G>C variant (also known as p.E1559Q) is located in coding exon 13 of the BRCA1 gene. This variant results from a G to C … (more)
The c.4675G>C variant (also known as p.E1559Q) is located in coding exon 13 of the BRCA1 gene. This variant results from a G to C substitution at nucleotide position 4675. The glutamic acid at codon 1559 is replaced by glutamine, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 13 which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA analysis showed that this alteration induces expression of a transcript lacking 11 nucleotides at the end of coding exon 13 (also called exon 15 in the literature-Ambry internal data; Davy G et al. Eur. J. Hum. Genet., 2017 10;25:1147-1154). Furthermore, a close match alteration at the same nucleotide position, BRCA1 c.4675G>A has been shown in multiple studies to have the same splice defect as this alteration (Wappenschmidt B et al. PLoS ONE, 2012 Dec; Wangensteen T et al. Hered Cancer Clin Pract, 2019 May;17:14; Koczkowska M et al. Cancers (Basel), 2018 Nov;10: ). This alteration was functional in a protein assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1) and is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145149.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Asian
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Laboratoire de Biologie et Génétique du Cancer, Centre François Baclesse
Accession: SCV000538190.1
First in ClinVar: May 27, 2015 Last updated: May 27, 2015 |
Sex: female
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Pathogenic
(May 05, 2023)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV003927191.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
The c.4738G>C variant (also known as p.Glu1580Gln) is located in coding exon 13 of the BRCA1 gene. This variant results from a G to C … (more)
The c.4738G>C variant (also known as p.Glu1580Gln) is located in coding exon 13 of the BRCA1 gene. This variant results from a G to C substitution at nucleotide position 4738. The glutamic acid at codon 1580 is replaced by glutamine, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 13 which makes it likely to have some effect on normal mRNA splicing. This alteration is predicted to decrease the efficiency of the native splice donor site by the BDGP and ESEfinder in silico models. RNA analysis showed that this alteration induces expression of a transcript lacking 11 nucleotides at the end of coding exon 13 (also called exon 15 in the literature-Davy G et al. Eur. J. Hum. Genet., 2017 10;25:1147-1154). Furthermore, a close match alteration at the same nucleotide position, BRCA1 c.4675G>A has been shown in multiple studies to have the same splice defect as this alteration (Wappenschmidt B et al. PLoS ONE, 2012 Dec; Wangensteen T et al. Hered Cancer Clin Pract, 2019 May;17:14; Koczkowska M et al. Cancers (Basel), 2018 Nov;10: ). This alteration was functional in a protein assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1) and is predicted to be tolerated by in silico analysis. ClinVar classifies this variant (37605) as pathogenic, rated 2 stars, with 6 submissions, 7 publications (15235020, 21394826, 23239986, 28781887, 28905878 and 2 more) and no conflicts. Therefore, this variant has been classified as pathogenic. (less)
Sex: female
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Likely pathogenic
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004243977.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Likely pathogenic
(Sep 13, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053786.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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effect on RNA splicing
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Laboratoire de Biologie et Génétique du Cancer, Centre François Baclesse
Accession: SCV000538190.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations. | Wangensteen T | Hereditary cancer in clinical practice | 2019 | PMID: 31143303 |
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients. | Koczkowska M | Cancers | 2018 | PMID: 30441849 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Expanding the spectrum of germline variants in cancer. | Siraj AK | Human genetics | 2017 | PMID: 28975465 |
Detecting splicing patterns in genes involved in hereditary breast and ovarian cancer. | Davy G | European journal of human genetics : EJHG | 2017 | PMID: 28905878 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Detection of Germline Mutation in Hereditary Breast and/or Ovarian Cancers by Next-Generation Sequencing on a Four-Gene Panel. | Kwong A | The Journal of molecular diagnostics : JMD | 2016 | PMID: 27157322 |
Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania. | Janavičius R | Cancer genetics | 2014 | PMID: 25066507 |
Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations. | Conner JR | Gynecologic oncology | 2014 | PMID: 24333842 |
Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction. | Wappenschmidt B | PloS one | 2012 | PMID: 23239986 |
Splicing and multifactorial analysis of intronic BRCA1 and BRCA2 sequence variants identifies clinically significant splicing aberrations up to 12 nucleotides from the intron/exon boundary. | Whiley PJ | Human mutation | 2011 | PMID: 21394826 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
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Text-mined citations for rs80356988 ...
HelpRecord last updated Sep 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.