Variant summary: BRCA1 c.4748G>C (p.Arg1583Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.7e-06 in 298824 control chromosomes (gnomAD database and Momozawa_2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4748G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (PTEN c.697C>T, p.Arg233X; in our internal database) for this variant, providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4748G>C (p.Arg1583Thr)
Germline
Classification
Help
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.
(3)
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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.
Uncertain significance
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4748G>C (p.Arg1583Thr)
Variation ID: 928766 Accession: VCV000928766.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43071166 (GRCh38) [ NCBI UCSC ] 17: 41223183 (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 Jun 22, 2020 Aug 11, 2024 Mar 20, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4748G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg1583Thr missense NM_001407571.1:c.4535G>C NP_001394500.1:p.Arg1512Thr missense NM_001407581.1:c.4814G>C NP_001394510.1:p.Arg1605Thr missense NM_001407582.1:c.4814G>C NP_001394511.1:p.Arg1605Thr missense NM_001407583.1:c.4811G>C NP_001394512.1:p.Arg1604Thr missense NM_001407585.1:c.4811G>C NP_001394514.1:p.Arg1604Thr missense NM_001407587.1:c.4811G>C NP_001394516.1:p.Arg1604Thr missense NM_001407590.1:c.4808G>C NP_001394519.1:p.Arg1603Thr missense NM_001407591.1:c.4808G>C NP_001394520.1:p.Arg1603Thr missense NM_001407593.1:c.4748G>C NP_001394522.1:p.Arg1583Thr missense NM_001407594.1:c.4748G>C NP_001394523.1:p.Arg1583Thr missense NM_001407596.1:c.4748G>C NP_001394525.1:p.Arg1583Thr missense NM_001407597.1:c.4748G>C NP_001394526.1:p.Arg1583Thr missense NM_001407598.1:c.4748G>C NP_001394527.1:p.Arg1583Thr missense NM_001407602.1:c.4748G>C NP_001394531.1:p.Arg1583Thr missense NM_001407603.1:c.4748G>C NP_001394532.1:p.Arg1583Thr missense NM_001407605.1:c.4748G>C NP_001394534.1:p.Arg1583Thr missense NM_001407610.1:c.4745G>C NP_001394539.1:p.Arg1582Thr missense NM_001407611.1:c.4745G>C NP_001394540.1:p.Arg1582Thr missense NM_001407612.1:c.4745G>C NP_001394541.1:p.Arg1582Thr missense NM_001407613.1:c.4745G>C NP_001394542.1:p.Arg1582Thr missense NM_001407614.1:c.4745G>C NP_001394543.1:p.Arg1582Thr missense NM_001407615.1:c.4745G>C NP_001394544.1:p.Arg1582Thr missense NM_001407616.1:c.4745G>C NP_001394545.1:p.Arg1582Thr missense NM_001407617.1:c.4745G>C NP_001394546.1:p.Arg1582Thr missense NM_001407618.1:c.4745G>C NP_001394547.1:p.Arg1582Thr missense NM_001407619.1:c.4745G>C NP_001394548.1:p.Arg1582Thr missense NM_001407620.1:c.4745G>C NP_001394549.1:p.Arg1582Thr missense NM_001407621.1:c.4745G>C NP_001394550.1:p.Arg1582Thr missense NM_001407622.1:c.4745G>C NP_001394551.1:p.Arg1582Thr missense NM_001407623.1:c.4745G>C NP_001394552.1:p.Arg1582Thr missense NM_001407624.1:c.4745G>C NP_001394553.1:p.Arg1582Thr missense NM_001407625.1:c.4745G>C NP_001394554.1:p.Arg1582Thr missense NM_001407626.1:c.4745G>C NP_001394555.1:p.Arg1582Thr missense NM_001407627.1:c.4742G>C NP_001394556.1:p.Arg1581Thr missense NM_001407628.1:c.4742G>C NP_001394557.1:p.Arg1581Thr missense NM_001407629.1:c.4742G>C NP_001394558.1:p.Arg1581Thr missense NM_001407630.1:c.4742G>C NP_001394559.1:p.Arg1581Thr missense NM_001407631.1:c.4742G>C NP_001394560.1:p.Arg1581Thr missense NM_001407632.1:c.4742G>C NP_001394561.1:p.Arg1581Thr missense NM_001407633.1:c.4742G>C NP_001394562.1:p.Arg1581Thr missense NM_001407634.1:c.4742G>C NP_001394563.1:p.Arg1581Thr missense NM_001407635.1:c.4742G>C NP_001394564.1:p.Arg1581Thr missense NM_001407636.1:c.4742G>C NP_001394565.1:p.Arg1581Thr missense NM_001407637.1:c.4742G>C NP_001394566.1:p.Arg1581Thr missense NM_001407638.1:c.4742G>C NP_001394567.1:p.Arg1581Thr missense NM_001407639.1:c.4742G>C NP_001394568.1:p.Arg1581Thr missense NM_001407640.1:c.4742G>C NP_001394569.1:p.Arg1581Thr missense NM_001407641.1:c.4742G>C NP_001394570.1:p.Arg1581Thr missense NM_001407642.1:c.4742G>C NP_001394571.1:p.Arg1581Thr missense NM_001407644.1:c.4739G>C NP_001394573.1:p.Arg1580Thr missense NM_001407645.1:c.4739G>C NP_001394574.1:p.Arg1580Thr missense NM_001407646.1:c.4736G>C NP_001394575.1:p.Arg1579Thr missense NM_001407647.1:c.4733G>C NP_001394576.1:p.Arg1578Thr missense NM_001407648.1:c.4691G>C NP_001394577.1:p.Arg1564Thr missense NM_001407649.1:c.4688G>C NP_001394578.1:p.Arg1563Thr missense NM_001407652.1:c.4748G>C NP_001394581.1:p.Arg1583Thr missense NM_001407653.1:c.4670G>C NP_001394582.1:p.Arg1557Thr missense NM_001407654.1:c.4670G>C NP_001394583.1:p.Arg1557Thr missense NM_001407655.1:c.4670G>C NP_001394584.1:p.Arg1557Thr missense NM_001407656.1:c.4667G>C NP_001394585.1:p.Arg1556Thr missense NM_001407657.1:c.4667G>C NP_001394586.1:p.Arg1556Thr missense NM_001407658.1:c.4667G>C NP_001394587.1:p.Arg1556Thr missense NM_001407659.1:c.4664G>C NP_001394588.1:p.Arg1555Thr missense NM_001407660.1:c.4664G>C NP_001394589.1:p.Arg1555Thr missense NM_001407661.1:c.4664G>C NP_001394590.1:p.Arg1555Thr missense NM_001407662.1:c.4664G>C NP_001394591.1:p.Arg1555Thr missense NM_001407663.1:c.4664G>C NP_001394592.1:p.Arg1555Thr missense NM_001407664.1:c.4625G>C NP_001394593.1:p.Arg1542Thr missense NM_001407665.1:c.4625G>C NP_001394594.1:p.Arg1542Thr missense NM_001407666.1:c.4625G>C NP_001394595.1:p.Arg1542Thr missense NM_001407667.1:c.4625G>C NP_001394596.1:p.Arg1542Thr missense NM_001407668.1:c.4625G>C NP_001394597.1:p.Arg1542Thr missense NM_001407669.1:c.4625G>C NP_001394598.1:p.Arg1542Thr missense NM_001407670.1:c.4622G>C NP_001394599.1:p.Arg1541Thr missense NM_001407671.1:c.4622G>C NP_001394600.1:p.Arg1541Thr missense NM_001407672.1:c.4622G>C NP_001394601.1:p.Arg1541Thr missense NM_001407673.1:c.4622G>C NP_001394602.1:p.Arg1541Thr missense NM_001407674.1:c.4622G>C NP_001394603.1:p.Arg1541Thr missense NM_001407675.1:c.4622G>C NP_001394604.1:p.Arg1541Thr missense NM_001407676.1:c.4622G>C NP_001394605.1:p.Arg1541Thr missense NM_001407677.1:c.4622G>C NP_001394606.1:p.Arg1541Thr missense NM_001407678.1:c.4622G>C NP_001394607.1:p.Arg1541Thr missense NM_001407679.1:c.4622G>C NP_001394608.1:p.Arg1541Thr missense NM_001407680.1:c.4622G>C NP_001394609.1:p.Arg1541Thr missense NM_001407681.1:c.4619G>C NP_001394610.1:p.Arg1540Thr missense NM_001407682.1:c.4619G>C NP_001394611.1:p.Arg1540Thr missense NM_001407683.1:c.4619G>C NP_001394612.1:p.Arg1540Thr missense NM_001407684.1:c.4748G>C NP_001394613.1:p.Arg1583Thr missense NM_001407685.1:c.4619G>C NP_001394614.1:p.Arg1540Thr missense NM_001407686.1:c.4619G>C NP_001394615.1:p.Arg1540Thr missense NM_001407687.1:c.4619G>C NP_001394616.1:p.Arg1540Thr missense NM_001407688.1:c.4619G>C NP_001394617.1:p.Arg1540Thr missense NM_001407689.1:c.4619G>C NP_001394618.1:p.Arg1540Thr missense NM_001407690.1:c.4616G>C NP_001394619.1:p.Arg1539Thr missense NM_001407691.1:c.4616G>C NP_001394620.1:p.Arg1539Thr missense NM_001407692.1:c.4607G>C NP_001394621.1:p.Arg1536Thr missense NM_001407694.1:c.4607G>C NP_001394623.1:p.Arg1536Thr missense NM_001407695.1:c.4607G>C NP_001394624.1:p.Arg1536Thr missense NM_001407696.1:c.4607G>C NP_001394625.1:p.Arg1536Thr missense NM_001407697.1:c.4607G>C NP_001394626.1:p.Arg1536Thr missense NM_001407698.1:c.4607G>C NP_001394627.1:p.Arg1536Thr missense NM_001407724.1:c.4607G>C NP_001394653.1:p.Arg1536Thr missense NM_001407725.1:c.4607G>C NP_001394654.1:p.Arg1536Thr missense NM_001407726.1:c.4607G>C NP_001394655.1:p.Arg1536Thr missense NM_001407727.1:c.4607G>C NP_001394656.1:p.Arg1536Thr missense NM_001407728.1:c.4607G>C NP_001394657.1:p.Arg1536Thr missense NM_001407729.1:c.4607G>C NP_001394658.1:p.Arg1536Thr missense NM_001407730.1:c.4607G>C NP_001394659.1:p.Arg1536Thr missense NM_001407731.1:c.4607G>C NP_001394660.1:p.Arg1536Thr missense NM_001407732.1:c.4604G>C NP_001394661.1:p.Arg1535Thr missense NM_001407733.1:c.4604G>C NP_001394662.1:p.Arg1535Thr missense NM_001407734.1:c.4604G>C NP_001394663.1:p.Arg1535Thr missense NM_001407735.1:c.4604G>C NP_001394664.1:p.Arg1535Thr missense NM_001407736.1:c.4604G>C NP_001394665.1:p.Arg1535Thr missense NM_001407737.1:c.4604G>C NP_001394666.1:p.Arg1535Thr missense NM_001407738.1:c.4604G>C NP_001394667.1:p.Arg1535Thr missense NM_001407739.1:c.4604G>C NP_001394668.1:p.Arg1535Thr missense NM_001407740.1:c.4604G>C NP_001394669.1:p.Arg1535Thr missense NM_001407741.1:c.4604G>C NP_001394670.1:p.Arg1535Thr missense NM_001407742.1:c.4604G>C NP_001394671.1:p.Arg1535Thr missense NM_001407743.1:c.4604G>C NP_001394672.1:p.Arg1535Thr missense NM_001407744.1:c.4604G>C NP_001394673.1:p.Arg1535Thr missense NM_001407745.1:c.4604G>C NP_001394674.1:p.Arg1535Thr missense NM_001407746.1:c.4604G>C NP_001394675.1:p.Arg1535Thr missense NM_001407747.1:c.4604G>C NP_001394676.1:p.Arg1535Thr missense NM_001407748.1:c.4604G>C NP_001394677.1:p.Arg1535Thr missense NM_001407749.1:c.4604G>C NP_001394678.1:p.Arg1535Thr missense NM_001407750.1:c.4604G>C NP_001394679.1:p.Arg1535Thr missense NM_001407751.1:c.4604G>C NP_001394680.1:p.Arg1535Thr missense NM_001407752.1:c.4604G>C NP_001394681.1:p.Arg1535Thr missense NM_001407838.1:c.4601G>C NP_001394767.1:p.Arg1534Thr missense NM_001407839.1:c.4601G>C NP_001394768.1:p.Arg1534Thr missense NM_001407841.1:c.4601G>C NP_001394770.1:p.Arg1534Thr missense NM_001407842.1:c.4601G>C NP_001394771.1:p.Arg1534Thr missense NM_001407843.1:c.4601G>C NP_001394772.1:p.Arg1534Thr missense NM_001407844.1:c.4601G>C NP_001394773.1:p.Arg1534Thr missense NM_001407845.1:c.4601G>C NP_001394774.1:p.Arg1534Thr missense NM_001407846.1:c.4601G>C NP_001394775.1:p.Arg1534Thr missense NM_001407847.1:c.4601G>C NP_001394776.1:p.Arg1534Thr missense NM_001407848.1:c.4601G>C NP_001394777.1:p.Arg1534Thr missense NM_001407849.1:c.4601G>C NP_001394778.1:p.Arg1534Thr missense NM_001407850.1:c.4601G>C NP_001394779.1:p.Arg1534Thr missense NM_001407851.1:c.4601G>C NP_001394780.1:p.Arg1534Thr missense NM_001407852.1:c.4601G>C NP_001394781.1:p.Arg1534Thr missense NM_001407853.1:c.4601G>C NP_001394782.1:p.Arg1534Thr missense NM_001407854.1:c.4748G>C NP_001394783.1:p.Arg1583Thr missense NM_001407858.1:c.4745G>C NP_001394787.1:p.Arg1582Thr missense NM_001407859.1:c.4745G>C NP_001394788.1:p.Arg1582Thr missense NM_001407860.1:c.4745G>C NP_001394789.1:p.Arg1582Thr missense NM_001407861.1:c.4742G>C NP_001394790.1:p.Arg1581Thr missense NM_001407862.1:c.4547G>C NP_001394791.1:p.Arg1516Thr missense NM_001407863.1:c.4622G>C NP_001394792.1:p.Arg1541Thr missense NM_001407874.1:c.4541G>C NP_001394803.1:p.Arg1514Thr missense NM_001407875.1:c.4541G>C NP_001394804.1:p.Arg1514Thr missense NM_001407879.1:c.4538G>C NP_001394808.1:p.Arg1513Thr missense NM_001407881.1:c.4538G>C NP_001394810.1:p.Arg1513Thr missense NM_001407882.1:c.4538G>C NP_001394811.1:p.Arg1513Thr missense NM_001407884.1:c.4538G>C NP_001394813.1:p.Arg1513Thr missense NM_001407885.1:c.4538G>C NP_001394814.1:p.Arg1513Thr missense NM_001407886.1:c.4538G>C NP_001394815.1:p.Arg1513Thr missense NM_001407887.1:c.4538G>C NP_001394816.1:p.Arg1513Thr missense NM_001407889.1:c.4538G>C NP_001394818.1:p.Arg1513Thr missense NM_001407894.1:c.4535G>C NP_001394823.1:p.Arg1512Thr missense NM_001407895.1:c.4535G>C NP_001394824.1:p.Arg1512Thr missense NM_001407896.1:c.4535G>C NP_001394825.1:p.Arg1512Thr missense NM_001407897.1:c.4535G>C NP_001394826.1:p.Arg1512Thr missense NM_001407898.1:c.4535G>C NP_001394827.1:p.Arg1512Thr missense NM_001407899.1:c.4535G>C NP_001394828.1:p.Arg1512Thr missense NM_001407900.1:c.4535G>C NP_001394829.1:p.Arg1512Thr missense NM_001407902.1:c.4535G>C NP_001394831.1:p.Arg1512Thr missense NM_001407904.1:c.4535G>C NP_001394833.1:p.Arg1512Thr missense NM_001407906.1:c.4535G>C NP_001394835.1:p.Arg1512Thr missense NM_001407907.1:c.4535G>C NP_001394836.1:p.Arg1512Thr missense NM_001407908.1:c.4535G>C NP_001394837.1:p.Arg1512Thr missense NM_001407909.1:c.4535G>C NP_001394838.1:p.Arg1512Thr missense NM_001407910.1:c.4535G>C NP_001394839.1:p.Arg1512Thr missense NM_001407915.1:c.4532G>C NP_001394844.1:p.Arg1511Thr missense NM_001407916.1:c.4532G>C NP_001394845.1:p.Arg1511Thr missense NM_001407917.1:c.4532G>C NP_001394846.1:p.Arg1511Thr missense NM_001407918.1:c.4532G>C NP_001394847.1:p.Arg1511Thr missense NM_001407919.1:c.4625G>C NP_001394848.1:p.Arg1542Thr missense NM_001407920.1:c.4484G>C NP_001394849.1:p.Arg1495Thr missense NM_001407921.1:c.4484G>C NP_001394850.1:p.Arg1495Thr missense NM_001407922.1:c.4484G>C NP_001394851.1:p.Arg1495Thr missense NM_001407923.1:c.4484G>C NP_001394852.1:p.Arg1495Thr missense NM_001407924.1:c.4484G>C NP_001394853.1:p.Arg1495Thr missense NM_001407925.1:c.4484G>C NP_001394854.1:p.Arg1495Thr missense NM_001407926.1:c.4484G>C NP_001394855.1:p.Arg1495Thr missense NM_001407927.1:c.4481G>C NP_001394856.1:p.Arg1494Thr missense NM_001407928.1:c.4481G>C NP_001394857.1:p.Arg1494Thr missense NM_001407929.1:c.4481G>C NP_001394858.1:p.Arg1494Thr missense NM_001407930.1:c.4481G>C NP_001394859.1:p.Arg1494Thr missense NM_001407931.1:c.4481G>C NP_001394860.1:p.Arg1494Thr missense NM_001407932.1:c.4481G>C NP_001394861.1:p.Arg1494Thr missense NM_001407933.1:c.4481G>C NP_001394862.1:p.Arg1494Thr missense NM_001407934.1:c.4478G>C NP_001394863.1:p.Arg1493Thr missense NM_001407935.1:c.4478G>C NP_001394864.1:p.Arg1493Thr missense NM_001407936.1:c.4478G>C NP_001394865.1:p.Arg1493Thr missense NM_001407937.1:c.4625G>C NP_001394866.1:p.Arg1542Thr missense NM_001407938.1:c.4625G>C NP_001394867.1:p.Arg1542Thr missense NM_001407939.1:c.4622G>C NP_001394868.1:p.Arg1541Thr missense NM_001407940.1:c.4622G>C NP_001394869.1:p.Arg1541Thr missense NM_001407941.1:c.4619G>C NP_001394870.1:p.Arg1540Thr missense NM_001407942.1:c.4607G>C NP_001394871.1:p.Arg1536Thr missense NM_001407943.1:c.4604G>C NP_001394872.1:p.Arg1535Thr missense NM_001407944.1:c.4604G>C NP_001394873.1:p.Arg1535Thr missense NM_001407945.1:c.4604G>C NP_001394874.1:p.Arg1535Thr missense NM_001407946.1:c.4415G>C NP_001394875.1:p.Arg1472Thr missense NM_001407947.1:c.4415G>C NP_001394876.1:p.Arg1472Thr missense NM_001407948.1:c.4415G>C NP_001394877.1:p.Arg1472Thr missense NM_001407949.1:c.4415G>C NP_001394878.1:p.Arg1472Thr missense NM_001407950.1:c.4412G>C NP_001394879.1:p.Arg1471Thr missense NM_001407951.1:c.4412G>C NP_001394880.1:p.Arg1471Thr missense NM_001407952.1:c.4412G>C NP_001394881.1:p.Arg1471Thr missense NM_001407953.1:c.4412G>C NP_001394882.1:p.Arg1471Thr missense NM_001407954.1:c.4412G>C NP_001394883.1:p.Arg1471Thr missense NM_001407955.1:c.4412G>C NP_001394884.1:p.Arg1471Thr missense NM_001407956.1:c.4409G>C NP_001394885.1:p.Arg1470Thr missense NM_001407957.1:c.4409G>C NP_001394886.1:p.Arg1470Thr missense NM_001407958.1:c.4409G>C NP_001394887.1:p.Arg1470Thr missense NM_001407959.1:c.4367G>C NP_001394888.1:p.Arg1456Thr missense NM_001407960.1:c.4364G>C NP_001394889.1:p.Arg1455Thr missense NM_001407962.1:c.4364G>C NP_001394891.1:p.Arg1455Thr missense NM_001407963.1:c.4361G>C NP_001394892.1:p.Arg1454Thr missense NM_001407964.1:c.4286G>C NP_001394893.1:p.Arg1429Thr missense NM_001407965.1:c.4241G>C NP_001394894.1:p.Arg1414Thr missense NM_001407966.1:c.3860G>C NP_001394895.1:p.Arg1287Thr missense NM_001407967.1:c.3857G>C NP_001394896.1:p.Arg1286Thr missense NM_001407968.1:c.2144G>C NP_001394897.1:p.Arg715Thr missense NM_001407969.1:c.2141G>C NP_001394898.1:p.Arg714Thr missense NM_001407970.1:c.1505G>C NP_001394899.1:p.Arg502Thr missense NM_001407971.1:c.1505G>C NP_001394900.1:p.Arg502Thr missense NM_001407972.1:c.1502G>C NP_001394901.1:p.Arg501Thr missense NM_001407973.1:c.1439G>C NP_001394902.1:p.Arg480Thr missense NM_001407974.1:c.1439G>C NP_001394903.1:p.Arg480Thr missense NM_001407975.1:c.1439G>C NP_001394904.1:p.Arg480Thr missense NM_001407976.1:c.1439G>C NP_001394905.1:p.Arg480Thr missense NM_001407977.1:c.1439G>C NP_001394906.1:p.Arg480Thr missense NM_001407978.1:c.1439G>C NP_001394907.1:p.Arg480Thr missense NM_001407979.1:c.1436G>C NP_001394908.1:p.Arg479Thr missense NM_001407980.1:c.1436G>C NP_001394909.1:p.Arg479Thr missense NM_001407981.1:c.1436G>C NP_001394910.1:p.Arg479Thr missense NM_001407982.1:c.1436G>C NP_001394911.1:p.Arg479Thr missense NM_001407983.1:c.1436G>C NP_001394912.1:p.Arg479Thr missense NM_001407984.1:c.1436G>C NP_001394913.1:p.Arg479Thr missense NM_001407985.1:c.1436G>C NP_001394914.1:p.Arg479Thr missense NM_001407986.1:c.1436G>C NP_001394915.1:p.Arg479Thr missense NM_001407990.1:c.1436G>C NP_001394919.1:p.Arg479Thr missense NM_001407991.1:c.1436G>C NP_001394920.1:p.Arg479Thr missense NM_001407992.1:c.1436G>C NP_001394921.1:p.Arg479Thr missense NM_001407993.1:c.1436G>C NP_001394922.1:p.Arg479Thr missense NM_001408392.1:c.1433G>C NP_001395321.1:p.Arg478Thr missense NM_001408396.1:c.1433G>C NP_001395325.1:p.Arg478Thr missense NM_001408397.1:c.1433G>C NP_001395326.1:p.Arg478Thr missense NM_001408398.1:c.1433G>C NP_001395327.1:p.Arg478Thr missense NM_001408399.1:c.1433G>C NP_001395328.1:p.Arg478Thr missense NM_001408400.1:c.1433G>C NP_001395329.1:p.Arg478Thr missense NM_001408401.1:c.1433G>C NP_001395330.1:p.Arg478Thr missense NM_001408402.1:c.1433G>C NP_001395331.1:p.Arg478Thr missense NM_001408403.1:c.1433G>C NP_001395332.1:p.Arg478Thr missense NM_001408404.1:c.1433G>C NP_001395333.1:p.Arg478Thr missense NM_001408406.1:c.1430G>C NP_001395335.1:p.Arg477Thr missense NM_001408407.1:c.1430G>C NP_001395336.1:p.Arg477Thr missense NM_001408408.1:c.1430G>C NP_001395337.1:p.Arg477Thr missense NM_001408409.1:c.1427G>C NP_001395338.1:p.Arg476Thr missense NM_001408410.1:c.1364G>C NP_001395339.1:p.Arg455Thr missense NM_001408411.1:c.1361G>C NP_001395340.1:p.Arg454Thr missense NM_001408412.1:c.1358G>C NP_001395341.1:p.Arg453Thr missense NM_001408413.1:c.1358G>C NP_001395342.1:p.Arg453Thr missense NM_001408414.1:c.1358G>C NP_001395343.1:p.Arg453Thr missense NM_001408415.1:c.1358G>C NP_001395344.1:p.Arg453Thr missense NM_001408416.1:c.1358G>C NP_001395345.1:p.Arg453Thr missense NM_001408418.1:c.1322G>C NP_001395347.1:p.Arg441Thr missense NM_001408419.1:c.1322G>C NP_001395348.1:p.Arg441Thr missense NM_001408420.1:c.1322G>C NP_001395349.1:p.Arg441Thr missense NM_001408421.1:c.1319G>C NP_001395350.1:p.Arg440Thr missense NM_001408422.1:c.1319G>C NP_001395351.1:p.Arg440Thr missense NM_001408423.1:c.1319G>C NP_001395352.1:p.Arg440Thr missense NM_001408424.1:c.1319G>C NP_001395353.1:p.Arg440Thr missense NM_001408425.1:c.1316G>C NP_001395354.1:p.Arg439Thr missense NM_001408426.1:c.1316G>C NP_001395355.1:p.Arg439Thr missense NM_001408427.1:c.1316G>C NP_001395356.1:p.Arg439Thr missense NM_001408428.1:c.1316G>C NP_001395357.1:p.Arg439Thr missense NM_001408429.1:c.1316G>C NP_001395358.1:p.Arg439Thr missense NM_001408430.1:c.1316G>C NP_001395359.1:p.Arg439Thr missense NM_001408431.1:c.1316G>C NP_001395360.1:p.Arg439Thr missense NM_001408432.1:c.1313G>C NP_001395361.1:p.Arg438Thr missense NM_001408433.1:c.1313G>C NP_001395362.1:p.Arg438Thr missense NM_001408434.1:c.1313G>C NP_001395363.1:p.Arg438Thr missense NM_001408435.1:c.1313G>C NP_001395364.1:p.Arg438Thr missense NM_001408436.1:c.1313G>C NP_001395365.1:p.Arg438Thr missense NM_001408437.1:c.1313G>C NP_001395366.1:p.Arg438Thr missense NM_001408438.1:c.1313G>C NP_001395367.1:p.Arg438Thr missense NM_001408439.1:c.1313G>C NP_001395368.1:p.Arg438Thr missense NM_001408440.1:c.1313G>C NP_001395369.1:p.Arg438Thr missense NM_001408441.1:c.1313G>C NP_001395370.1:p.Arg438Thr missense NM_001408442.1:c.1313G>C NP_001395371.1:p.Arg438Thr missense NM_001408443.1:c.1313G>C NP_001395372.1:p.Arg438Thr missense NM_001408444.1:c.1313G>C NP_001395373.1:p.Arg438Thr missense NM_001408445.1:c.1310G>C NP_001395374.1:p.Arg437Thr missense NM_001408446.1:c.1310G>C NP_001395375.1:p.Arg437Thr missense NM_001408447.1:c.1310G>C NP_001395376.1:p.Arg437Thr missense NM_001408448.1:c.1310G>C NP_001395377.1:p.Arg437Thr missense NM_001408450.1:c.1310G>C NP_001395379.1:p.Arg437Thr missense NM_001408451.1:c.1304G>C NP_001395380.1:p.Arg435Thr missense NM_001408452.1:c.1298G>C NP_001395381.1:p.Arg433Thr missense NM_001408453.1:c.1298G>C NP_001395382.1:p.Arg433Thr missense NM_001408454.1:c.1298G>C NP_001395383.1:p.Arg433Thr missense NM_001408455.1:c.1298G>C NP_001395384.1:p.Arg433Thr missense NM_001408456.1:c.1298G>C NP_001395385.1:p.Arg433Thr missense NM_001408457.1:c.1298G>C NP_001395386.1:p.Arg433Thr missense NM_001408458.1:c.1295G>C NP_001395387.1:p.Arg432Thr missense NM_001408459.1:c.1295G>C NP_001395388.1:p.Arg432Thr missense NM_001408460.1:c.1295G>C NP_001395389.1:p.Arg432Thr missense NM_001408461.1:c.1295G>C NP_001395390.1:p.Arg432Thr missense NM_001408462.1:c.1295G>C NP_001395391.1:p.Arg432Thr missense NM_001408463.1:c.1295G>C NP_001395392.1:p.Arg432Thr missense NM_001408464.1:c.1295G>C NP_001395393.1:p.Arg432Thr missense NM_001408465.1:c.1295G>C NP_001395394.1:p.Arg432Thr missense NM_001408466.1:c.1295G>C NP_001395395.1:p.Arg432Thr missense NM_001408467.1:c.1295G>C NP_001395396.1:p.Arg432Thr missense NM_001408468.1:c.1292G>C NP_001395397.1:p.Arg431Thr missense NM_001408469.1:c.1292G>C NP_001395398.1:p.Arg431Thr missense NM_001408470.1:c.1292G>C NP_001395399.1:p.Arg431Thr missense NM_001408472.1:c.1436G>C NP_001395401.1:p.Arg479Thr missense NM_001408473.1:c.1433G>C NP_001395402.1:p.Arg478Thr missense NM_001408474.1:c.1238G>C NP_001395403.1:p.Arg413Thr missense NM_001408475.1:c.1235G>C NP_001395404.1:p.Arg412Thr missense NM_001408476.1:c.1235G>C NP_001395405.1:p.Arg412Thr missense NM_001408478.1:c.1229G>C NP_001395407.1:p.Arg410Thr missense NM_001408479.1:c.1229G>C NP_001395408.1:p.Arg410Thr missense NM_001408480.1:c.1229G>C NP_001395409.1:p.Arg410Thr missense NM_001408481.1:c.1226G>C NP_001395410.1:p.Arg409Thr missense NM_001408482.1:c.1226G>C NP_001395411.1:p.Arg409Thr missense NM_001408483.1:c.1226G>C NP_001395412.1:p.Arg409Thr missense NM_001408484.1:c.1226G>C NP_001395413.1:p.Arg409Thr missense NM_001408485.1:c.1226G>C NP_001395414.1:p.Arg409Thr missense NM_001408489.1:c.1226G>C NP_001395418.1:p.Arg409Thr missense NM_001408490.1:c.1226G>C NP_001395419.1:p.Arg409Thr missense NM_001408491.1:c.1226G>C NP_001395420.1:p.Arg409Thr missense NM_001408492.1:c.1223G>C NP_001395421.1:p.Arg408Thr missense NM_001408493.1:c.1223G>C NP_001395422.1:p.Arg408Thr missense NM_001408494.1:c.1199G>C NP_001395423.1:p.Arg400Thr missense NM_001408495.1:c.1193G>C NP_001395424.1:p.Arg398Thr missense NM_001408496.1:c.1175G>C NP_001395425.1:p.Arg392Thr missense NM_001408497.1:c.1175G>C NP_001395426.1:p.Arg392Thr missense NM_001408498.1:c.1175G>C NP_001395427.1:p.Arg392Thr missense NM_001408499.1:c.1175G>C NP_001395428.1:p.Arg392Thr missense NM_001408500.1:c.1175G>C NP_001395429.1:p.Arg392Thr missense NM_001408501.1:c.1175G>C NP_001395430.1:p.Arg392Thr missense NM_001408502.1:c.1172G>C NP_001395431.1:p.Arg391Thr missense NM_001408503.1:c.1172G>C NP_001395432.1:p.Arg391Thr missense NM_001408504.1:c.1172G>C NP_001395433.1:p.Arg391Thr missense NM_001408505.1:c.1169G>C NP_001395434.1:p.Arg390Thr missense NM_001408506.1:c.1112G>C NP_001395435.1:p.Arg371Thr missense NM_001408507.1:c.1109G>C NP_001395436.1:p.Arg370Thr missense NM_001408508.1:c.1100G>C NP_001395437.1:p.Arg367Thr missense NM_001408509.1:c.1097G>C NP_001395438.1:p.Arg366Thr missense NM_001408510.1:c.1058G>C NP_001395439.1:p.Arg353Thr missense NM_001408511.1:c.1055G>C NP_001395440.1:p.Arg352Thr missense NM_001408512.1:c.935G>C NP_001395441.1:p.Arg312Thr missense NM_001408513.1:c.908G>C NP_001395442.1:p.Arg303Thr missense NM_007297.4:c.4607G>C NP_009228.2:p.Arg1536Thr missense NM_007298.4:c.1436G>C NP_009229.2:p.Arg479Thr missense NM_007299.4:c.1436G>C NP_009230.2:p.Arg479Thr missense NM_007300.4:c.4811G>C NP_009231.2:p.Arg1604Thr missense NM_007304.2:c.1436G>C NP_009235.2:p.Arg479Thr missense NR_027676.2:n.4925G>C non-coding transcript variant NC_000017.11:g.43071166C>G NC_000017.10:g.41223183C>G NG_005905.2:g.146818G>C LRG_292:g.146818G>C LRG_292t1:c.4748G>C LRG_292p1:p.Arg1583Thr - Protein change
- R1536T, R1583T, R1604T, R479T, R1472T, R1495T, R1513T, R1542T, R1557T, R1578T, R1580T, R1605T, R312T, R352T, R398T, R408T, R440T, R476T, R477T, R501T, R1287T, R1454T, R1456T, R1471T, R1511T, R1514T, R1556T, R1564T, R1581T, R1582T, R366T, R390T, R400T, R410T, R413T, R432T, R433T, R455T, R478T, R480T, R502T, R714T, R715T, R1286T, R1414T, R1455T, R1493T, R1512T, R1516T, R1540T, R1555T, R1603T, R303T, R353T, R367T, R370T, R371T, R392T, R412T, R437T, R438T, R439T, R441T, R1429T, R1470T, R1494T, R1534T, R1535T, R1539T, R1541T, R1563T, R1579T, R391T, R409T, R431T, R435T, R453T, R454T
- Other names
- -
- Canonical SPDI
- NC_000017.11:43071165:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
- Links
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 |
13041 | 14847 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 18, 2019 | RCV001193162.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 6, 2021 | RCV001859168.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 20, 2024 | RCV004601382.1 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jul 18, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361838.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRCA1 c.4748G>C (p.Arg1583Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.4748G>C (p.Arg1583Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.7e-06 in 298824 control chromosomes (gnomAD database and Momozawa_2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4748G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (PTEN c.697C>T, p.Arg233X; in our internal database) for this variant, providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
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Uncertain significance
(Sep 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002303460.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 928766). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 1583 of the BRCA1 protein (p.Arg1583Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine. (less)
|
|
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Uncertain significance
(Mar 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV005100973.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
The p.R1583T variant (also known as c.4748G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide … (more)
The p.R1583T variant (also known as c.4748G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4748. The arginine at codon 1583 is replaced by threonine, an amino acid with similar properties. This variant was not observed in 7051 unselected female breast cancer patients but was detected in 2/11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083). This variant was found to be functional in homology-directed repair functional assay (Adamovich AI et al. Am J Hum Genet, 2022 Apr;109:618-630). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. (less)
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Comment:
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 928766). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 1583 of the BRCA1 protein (p.Arg1583Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine.
Comment:
The p.R1583T variant (also known as c.4748G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4748. The arginine at codon 1583 is replaced by threonine, an amino acid with similar properties. This variant was not observed in 7051 unselected female breast cancer patients but was detected in 2/11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083). This variant was found to be functional in homology-directed repair functional assay (Adamovich AI et al. Am J Hum Genet, 2022 Apr;109:618-630). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: BRCA1 c.4748G>C (p.Arg1583Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.7e-06 in 298824 control chromosomes (gnomAD database and Momozawa_2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4748G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (PTEN c.697C>T, p.Arg233X; in our internal database) for this variant, providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 928766). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 1583 of the BRCA1 protein (p.Arg1583Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine.
Comment:
The p.R1583T variant (also known as c.4748G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4748. The arginine at codon 1583 is replaced by threonine, an amino acid with similar properties. This variant was not observed in 7051 unselected female breast cancer patients but was detected in 2/11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083). This variant was found to be functional in homology-directed repair functional assay (Adamovich AI et al. Am J Hum Genet, 2022 Apr;109:618-630). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The functional impact of BRCA1 BRCT domain variants using multiplexed DNA double-strand break repair assays. | Adamovich AI | American journal of human genetics | 2022 | PMID: 35196514 |
| Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Text-mined citations for rs752624544 ...
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Record last updated Sep 29, 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.