The p.D1557N variant (also known as c.4669G>A), located in coding exon 13 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4669. The aspartic acid at codon 1557 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4669G>A (p.Asp1557Asn)
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.
(2)
Help
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
2
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.4669G>A (p.Asp1557Asn)
Variation ID: 441446 Accession: VCV000441446.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074337 (GRCh38) [ NCBI UCSC ] 17: 41226354 (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 Oct 23, 2017 May 1, 2024 Jun 19, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4669G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asp1557Asn missense NM_001407571.1:c.4456G>A NP_001394500.1:p.Asp1486Asn missense NM_001407581.1:c.4735G>A NP_001394510.1:p.Asp1579Asn missense NM_001407582.1:c.4735G>A NP_001394511.1:p.Asp1579Asn missense NM_001407583.1:c.4732G>A NP_001394512.1:p.Asp1578Asn missense NM_001407585.1:c.4732G>A NP_001394514.1:p.Asp1578Asn missense NM_001407587.1:c.4732G>A NP_001394516.1:p.Asp1578Asn missense NM_001407590.1:c.4729G>A NP_001394519.1:p.Asp1577Asn missense NM_001407591.1:c.4729G>A NP_001394520.1:p.Asp1577Asn missense NM_001407593.1:c.4669G>A NP_001394522.1:p.Asp1557Asn missense NM_001407594.1:c.4669G>A NP_001394523.1:p.Asp1557Asn missense NM_001407596.1:c.4669G>A NP_001394525.1:p.Asp1557Asn missense NM_001407597.1:c.4669G>A NP_001394526.1:p.Asp1557Asn missense NM_001407598.1:c.4669G>A NP_001394527.1:p.Asp1557Asn missense NM_001407602.1:c.4669G>A NP_001394531.1:p.Asp1557Asn missense NM_001407603.1:c.4669G>A NP_001394532.1:p.Asp1557Asn missense NM_001407605.1:c.4669G>A NP_001394534.1:p.Asp1557Asn missense NM_001407610.1:c.4666G>A NP_001394539.1:p.Asp1556Asn missense NM_001407611.1:c.4666G>A NP_001394540.1:p.Asp1556Asn missense NM_001407612.1:c.4666G>A NP_001394541.1:p.Asp1556Asn missense NM_001407613.1:c.4666G>A NP_001394542.1:p.Asp1556Asn missense NM_001407614.1:c.4666G>A NP_001394543.1:p.Asp1556Asn missense NM_001407615.1:c.4666G>A NP_001394544.1:p.Asp1556Asn missense NM_001407616.1:c.4666G>A NP_001394545.1:p.Asp1556Asn missense NM_001407617.1:c.4666G>A NP_001394546.1:p.Asp1556Asn missense NM_001407618.1:c.4666G>A NP_001394547.1:p.Asp1556Asn missense NM_001407619.1:c.4666G>A NP_001394548.1:p.Asp1556Asn missense NM_001407620.1:c.4666G>A NP_001394549.1:p.Asp1556Asn missense NM_001407621.1:c.4666G>A NP_001394550.1:p.Asp1556Asn missense NM_001407622.1:c.4666G>A NP_001394551.1:p.Asp1556Asn missense NM_001407623.1:c.4666G>A NP_001394552.1:p.Asp1556Asn missense NM_001407624.1:c.4666G>A NP_001394553.1:p.Asp1556Asn missense NM_001407625.1:c.4666G>A NP_001394554.1:p.Asp1556Asn missense NM_001407626.1:c.4666G>A NP_001394555.1:p.Asp1556Asn missense NM_001407627.1:c.4663G>A NP_001394556.1:p.Asp1555Asn missense NM_001407628.1:c.4663G>A NP_001394557.1:p.Asp1555Asn missense NM_001407629.1:c.4663G>A NP_001394558.1:p.Asp1555Asn missense NM_001407630.1:c.4663G>A NP_001394559.1:p.Asp1555Asn missense NM_001407631.1:c.4663G>A NP_001394560.1:p.Asp1555Asn missense NM_001407632.1:c.4663G>A NP_001394561.1:p.Asp1555Asn missense NM_001407633.1:c.4663G>A NP_001394562.1:p.Asp1555Asn missense NM_001407634.1:c.4663G>A NP_001394563.1:p.Asp1555Asn missense NM_001407635.1:c.4663G>A NP_001394564.1:p.Asp1555Asn missense NM_001407636.1:c.4663G>A NP_001394565.1:p.Asp1555Asn missense NM_001407637.1:c.4663G>A NP_001394566.1:p.Asp1555Asn missense NM_001407638.1:c.4663G>A NP_001394567.1:p.Asp1555Asn missense NM_001407639.1:c.4663G>A NP_001394568.1:p.Asp1555Asn missense NM_001407640.1:c.4663G>A NP_001394569.1:p.Asp1555Asn missense NM_001407641.1:c.4663G>A NP_001394570.1:p.Asp1555Asn missense NM_001407642.1:c.4663G>A NP_001394571.1:p.Asp1555Asn missense NM_001407644.1:c.4660G>A NP_001394573.1:p.Asp1554Asn missense NM_001407645.1:c.4660G>A NP_001394574.1:p.Asp1554Asn missense NM_001407646.1:c.4657G>A NP_001394575.1:p.Asp1553Asn missense NM_001407647.1:c.4654G>A NP_001394576.1:p.Asp1552Asn missense NM_001407648.1:c.4612G>A NP_001394577.1:p.Asp1538Asn missense NM_001407649.1:c.4609G>A NP_001394578.1:p.Asp1537Asn missense NM_001407652.1:c.4669G>A NP_001394581.1:p.Asp1557Asn missense NM_001407653.1:c.4591G>A NP_001394582.1:p.Asp1531Asn missense NM_001407654.1:c.4591G>A NP_001394583.1:p.Asp1531Asn missense NM_001407655.1:c.4591G>A NP_001394584.1:p.Asp1531Asn missense NM_001407656.1:c.4588G>A NP_001394585.1:p.Asp1530Asn missense NM_001407657.1:c.4588G>A NP_001394586.1:p.Asp1530Asn missense NM_001407658.1:c.4588G>A NP_001394587.1:p.Asp1530Asn missense NM_001407659.1:c.4585G>A NP_001394588.1:p.Asp1529Asn missense NM_001407660.1:c.4585G>A NP_001394589.1:p.Asp1529Asn missense NM_001407661.1:c.4585G>A NP_001394590.1:p.Asp1529Asn missense NM_001407662.1:c.4585G>A NP_001394591.1:p.Asp1529Asn missense NM_001407663.1:c.4585G>A NP_001394592.1:p.Asp1529Asn missense NM_001407664.1:c.4546G>A NP_001394593.1:p.Asp1516Asn missense NM_001407665.1:c.4546G>A NP_001394594.1:p.Asp1516Asn missense NM_001407666.1:c.4546G>A NP_001394595.1:p.Asp1516Asn missense NM_001407667.1:c.4546G>A NP_001394596.1:p.Asp1516Asn missense NM_001407668.1:c.4546G>A NP_001394597.1:p.Asp1516Asn missense NM_001407669.1:c.4546G>A NP_001394598.1:p.Asp1516Asn missense NM_001407670.1:c.4543G>A NP_001394599.1:p.Asp1515Asn missense NM_001407671.1:c.4543G>A NP_001394600.1:p.Asp1515Asn missense NM_001407672.1:c.4543G>A NP_001394601.1:p.Asp1515Asn missense NM_001407673.1:c.4543G>A NP_001394602.1:p.Asp1515Asn missense NM_001407674.1:c.4543G>A NP_001394603.1:p.Asp1515Asn missense NM_001407675.1:c.4543G>A NP_001394604.1:p.Asp1515Asn missense NM_001407676.1:c.4543G>A NP_001394605.1:p.Asp1515Asn missense NM_001407677.1:c.4543G>A NP_001394606.1:p.Asp1515Asn missense NM_001407678.1:c.4543G>A NP_001394607.1:p.Asp1515Asn missense NM_001407679.1:c.4543G>A NP_001394608.1:p.Asp1515Asn missense NM_001407680.1:c.4543G>A NP_001394609.1:p.Asp1515Asn missense NM_001407681.1:c.4540G>A NP_001394610.1:p.Asp1514Asn missense NM_001407682.1:c.4540G>A NP_001394611.1:p.Asp1514Asn missense NM_001407683.1:c.4540G>A NP_001394612.1:p.Asp1514Asn missense NM_001407684.1:c.4669G>A NP_001394613.1:p.Asp1557Asn missense NM_001407685.1:c.4540G>A NP_001394614.1:p.Asp1514Asn missense NM_001407686.1:c.4540G>A NP_001394615.1:p.Asp1514Asn missense NM_001407687.1:c.4540G>A NP_001394616.1:p.Asp1514Asn missense NM_001407688.1:c.4540G>A NP_001394617.1:p.Asp1514Asn missense NM_001407689.1:c.4540G>A NP_001394618.1:p.Asp1514Asn missense NM_001407690.1:c.4537G>A NP_001394619.1:p.Asp1513Asn missense NM_001407691.1:c.4537G>A NP_001394620.1:p.Asp1513Asn missense NM_001407692.1:c.4528G>A NP_001394621.1:p.Asp1510Asn missense NM_001407694.1:c.4528G>A NP_001394623.1:p.Asp1510Asn missense NM_001407695.1:c.4528G>A NP_001394624.1:p.Asp1510Asn missense NM_001407696.1:c.4528G>A NP_001394625.1:p.Asp1510Asn missense NM_001407697.1:c.4528G>A NP_001394626.1:p.Asp1510Asn missense NM_001407698.1:c.4528G>A NP_001394627.1:p.Asp1510Asn missense NM_001407724.1:c.4528G>A NP_001394653.1:p.Asp1510Asn missense NM_001407725.1:c.4528G>A NP_001394654.1:p.Asp1510Asn missense NM_001407726.1:c.4528G>A NP_001394655.1:p.Asp1510Asn missense NM_001407727.1:c.4528G>A NP_001394656.1:p.Asp1510Asn missense NM_001407728.1:c.4528G>A NP_001394657.1:p.Asp1510Asn missense NM_001407729.1:c.4528G>A NP_001394658.1:p.Asp1510Asn missense NM_001407730.1:c.4528G>A NP_001394659.1:p.Asp1510Asn missense NM_001407731.1:c.4528G>A NP_001394660.1:p.Asp1510Asn missense NM_001407732.1:c.4525G>A NP_001394661.1:p.Asp1509Asn missense NM_001407733.1:c.4525G>A NP_001394662.1:p.Asp1509Asn missense NM_001407734.1:c.4525G>A NP_001394663.1:p.Asp1509Asn missense NM_001407735.1:c.4525G>A NP_001394664.1:p.Asp1509Asn missense NM_001407736.1:c.4525G>A NP_001394665.1:p.Asp1509Asn missense NM_001407737.1:c.4525G>A NP_001394666.1:p.Asp1509Asn missense NM_001407738.1:c.4525G>A NP_001394667.1:p.Asp1509Asn missense NM_001407739.1:c.4525G>A NP_001394668.1:p.Asp1509Asn missense NM_001407740.1:c.4525G>A NP_001394669.1:p.Asp1509Asn missense NM_001407741.1:c.4525G>A NP_001394670.1:p.Asp1509Asn missense NM_001407742.1:c.4525G>A NP_001394671.1:p.Asp1509Asn missense NM_001407743.1:c.4525G>A NP_001394672.1:p.Asp1509Asn missense NM_001407744.1:c.4525G>A NP_001394673.1:p.Asp1509Asn missense NM_001407745.1:c.4525G>A NP_001394674.1:p.Asp1509Asn missense NM_001407746.1:c.4525G>A NP_001394675.1:p.Asp1509Asn missense NM_001407747.1:c.4525G>A NP_001394676.1:p.Asp1509Asn missense NM_001407748.1:c.4525G>A NP_001394677.1:p.Asp1509Asn missense NM_001407749.1:c.4525G>A NP_001394678.1:p.Asp1509Asn missense NM_001407750.1:c.4525G>A NP_001394679.1:p.Asp1509Asn missense NM_001407751.1:c.4525G>A NP_001394680.1:p.Asp1509Asn missense NM_001407752.1:c.4525G>A NP_001394681.1:p.Asp1509Asn missense NM_001407838.1:c.4522G>A NP_001394767.1:p.Asp1508Asn missense NM_001407839.1:c.4522G>A NP_001394768.1:p.Asp1508Asn missense NM_001407841.1:c.4522G>A NP_001394770.1:p.Asp1508Asn missense NM_001407842.1:c.4522G>A NP_001394771.1:p.Asp1508Asn missense NM_001407843.1:c.4522G>A NP_001394772.1:p.Asp1508Asn missense NM_001407844.1:c.4522G>A NP_001394773.1:p.Asp1508Asn missense NM_001407845.1:c.4522G>A NP_001394774.1:p.Asp1508Asn missense NM_001407846.1:c.4522G>A NP_001394775.1:p.Asp1508Asn missense NM_001407847.1:c.4522G>A NP_001394776.1:p.Asp1508Asn missense NM_001407848.1:c.4522G>A NP_001394777.1:p.Asp1508Asn missense NM_001407849.1:c.4522G>A NP_001394778.1:p.Asp1508Asn missense NM_001407850.1:c.4522G>A NP_001394779.1:p.Asp1508Asn missense NM_001407851.1:c.4522G>A NP_001394780.1:p.Asp1508Asn missense NM_001407852.1:c.4522G>A NP_001394781.1:p.Asp1508Asn missense NM_001407853.1:c.4522G>A NP_001394782.1:p.Asp1508Asn missense NM_001407854.1:c.4669G>A NP_001394783.1:p.Asp1557Asn missense NM_001407858.1:c.4666G>A NP_001394787.1:p.Asp1556Asn missense NM_001407859.1:c.4666G>A NP_001394788.1:p.Asp1556Asn missense NM_001407860.1:c.4666G>A NP_001394789.1:p.Asp1556Asn missense NM_001407861.1:c.4663G>A NP_001394790.1:p.Asp1555Asn missense NM_001407862.1:c.4468G>A NP_001394791.1:p.Asp1490Asn missense NM_001407863.1:c.4543G>A NP_001394792.1:p.Asp1515Asn missense NM_001407874.1:c.4462G>A NP_001394803.1:p.Asp1488Asn missense NM_001407875.1:c.4462G>A NP_001394804.1:p.Asp1488Asn missense NM_001407879.1:c.4459G>A NP_001394808.1:p.Asp1487Asn missense NM_001407881.1:c.4459G>A NP_001394810.1:p.Asp1487Asn missense NM_001407882.1:c.4459G>A NP_001394811.1:p.Asp1487Asn missense NM_001407884.1:c.4459G>A NP_001394813.1:p.Asp1487Asn missense NM_001407885.1:c.4459G>A NP_001394814.1:p.Asp1487Asn missense NM_001407886.1:c.4459G>A NP_001394815.1:p.Asp1487Asn missense NM_001407887.1:c.4459G>A NP_001394816.1:p.Asp1487Asn missense NM_001407889.1:c.4459G>A NP_001394818.1:p.Asp1487Asn missense NM_001407894.1:c.4456G>A NP_001394823.1:p.Asp1486Asn missense NM_001407895.1:c.4456G>A NP_001394824.1:p.Asp1486Asn missense NM_001407896.1:c.4456G>A NP_001394825.1:p.Asp1486Asn missense NM_001407897.1:c.4456G>A NP_001394826.1:p.Asp1486Asn missense NM_001407898.1:c.4456G>A NP_001394827.1:p.Asp1486Asn missense NM_001407899.1:c.4456G>A NP_001394828.1:p.Asp1486Asn missense NM_001407900.1:c.4456G>A NP_001394829.1:p.Asp1486Asn missense NM_001407902.1:c.4456G>A NP_001394831.1:p.Asp1486Asn missense NM_001407904.1:c.4456G>A NP_001394833.1:p.Asp1486Asn missense NM_001407906.1:c.4456G>A NP_001394835.1:p.Asp1486Asn missense NM_001407907.1:c.4456G>A NP_001394836.1:p.Asp1486Asn missense NM_001407908.1:c.4456G>A NP_001394837.1:p.Asp1486Asn missense NM_001407909.1:c.4456G>A NP_001394838.1:p.Asp1486Asn missense NM_001407910.1:c.4456G>A NP_001394839.1:p.Asp1486Asn missense NM_001407915.1:c.4453G>A NP_001394844.1:p.Asp1485Asn missense NM_001407916.1:c.4453G>A NP_001394845.1:p.Asp1485Asn missense NM_001407917.1:c.4453G>A NP_001394846.1:p.Asp1485Asn missense NM_001407918.1:c.4453G>A NP_001394847.1:p.Asp1485Asn missense NM_001407919.1:c.4546G>A NP_001394848.1:p.Asp1516Asn missense NM_001407920.1:c.4405G>A NP_001394849.1:p.Asp1469Asn missense NM_001407921.1:c.4405G>A NP_001394850.1:p.Asp1469Asn missense NM_001407922.1:c.4405G>A NP_001394851.1:p.Asp1469Asn missense NM_001407923.1:c.4405G>A NP_001394852.1:p.Asp1469Asn missense NM_001407924.1:c.4405G>A NP_001394853.1:p.Asp1469Asn missense NM_001407925.1:c.4405G>A NP_001394854.1:p.Asp1469Asn missense NM_001407926.1:c.4405G>A NP_001394855.1:p.Asp1469Asn missense NM_001407927.1:c.4402G>A NP_001394856.1:p.Asp1468Asn missense NM_001407928.1:c.4402G>A NP_001394857.1:p.Asp1468Asn missense NM_001407929.1:c.4402G>A NP_001394858.1:p.Asp1468Asn missense NM_001407930.1:c.4402G>A NP_001394859.1:p.Asp1468Asn missense NM_001407931.1:c.4402G>A NP_001394860.1:p.Asp1468Asn missense NM_001407932.1:c.4402G>A NP_001394861.1:p.Asp1468Asn missense NM_001407933.1:c.4402G>A NP_001394862.1:p.Asp1468Asn missense NM_001407934.1:c.4399G>A NP_001394863.1:p.Asp1467Asn missense NM_001407935.1:c.4399G>A NP_001394864.1:p.Asp1467Asn missense NM_001407936.1:c.4399G>A NP_001394865.1:p.Asp1467Asn missense NM_001407937.1:c.4546G>A NP_001394866.1:p.Asp1516Asn missense NM_001407938.1:c.4546G>A NP_001394867.1:p.Asp1516Asn missense NM_001407939.1:c.4543G>A NP_001394868.1:p.Asp1515Asn missense NM_001407940.1:c.4543G>A NP_001394869.1:p.Asp1515Asn missense NM_001407941.1:c.4540G>A NP_001394870.1:p.Asp1514Asn missense NM_001407942.1:c.4528G>A NP_001394871.1:p.Asp1510Asn missense NM_001407943.1:c.4525G>A NP_001394872.1:p.Asp1509Asn missense NM_001407944.1:c.4525G>A NP_001394873.1:p.Asp1509Asn missense NM_001407945.1:c.4525G>A NP_001394874.1:p.Asp1509Asn missense NM_001407946.1:c.4336G>A NP_001394875.1:p.Asp1446Asn missense NM_001407947.1:c.4336G>A NP_001394876.1:p.Asp1446Asn missense NM_001407948.1:c.4336G>A NP_001394877.1:p.Asp1446Asn missense NM_001407949.1:c.4336G>A NP_001394878.1:p.Asp1446Asn missense NM_001407950.1:c.4333G>A NP_001394879.1:p.Asp1445Asn missense NM_001407951.1:c.4333G>A NP_001394880.1:p.Asp1445Asn missense NM_001407952.1:c.4333G>A NP_001394881.1:p.Asp1445Asn missense NM_001407953.1:c.4333G>A NP_001394882.1:p.Asp1445Asn missense NM_001407954.1:c.4333G>A NP_001394883.1:p.Asp1445Asn missense NM_001407955.1:c.4333G>A NP_001394884.1:p.Asp1445Asn missense NM_001407956.1:c.4330G>A NP_001394885.1:p.Asp1444Asn missense NM_001407957.1:c.4330G>A NP_001394886.1:p.Asp1444Asn missense NM_001407958.1:c.4330G>A NP_001394887.1:p.Asp1444Asn missense NM_001407959.1:c.4288G>A NP_001394888.1:p.Asp1430Asn missense NM_001407960.1:c.4285G>A NP_001394889.1:p.Asp1429Asn missense NM_001407962.1:c.4285G>A NP_001394891.1:p.Asp1429Asn missense NM_001407963.1:c.4282G>A NP_001394892.1:p.Asp1428Asn missense NM_001407965.1:c.4162G>A NP_001394894.1:p.Asp1388Asn missense NM_001407966.1:c.3781G>A NP_001394895.1:p.Asp1261Asn missense NM_001407967.1:c.3778G>A NP_001394896.1:p.Asp1260Asn missense NM_001407968.1:c.2065G>A NP_001394897.1:p.Asp689Asn missense NM_001407969.1:c.2062G>A NP_001394898.1:p.Asp688Asn missense NM_001407970.1:c.1426G>A NP_001394899.1:p.Asp476Asn missense NM_001407971.1:c.1426G>A NP_001394900.1:p.Asp476Asn missense NM_001407972.1:c.1423G>A NP_001394901.1:p.Asp475Asn missense NM_001407973.1:c.1360G>A NP_001394902.1:p.Asp454Asn missense NM_001407974.1:c.1360G>A NP_001394903.1:p.Asp454Asn missense NM_001407975.1:c.1360G>A NP_001394904.1:p.Asp454Asn missense NM_001407976.1:c.1360G>A NP_001394905.1:p.Asp454Asn missense NM_001407977.1:c.1360G>A NP_001394906.1:p.Asp454Asn missense NM_001407978.1:c.1360G>A NP_001394907.1:p.Asp454Asn missense NM_001407979.1:c.1357G>A NP_001394908.1:p.Asp453Asn missense NM_001407980.1:c.1357G>A NP_001394909.1:p.Asp453Asn missense NM_001407981.1:c.1357G>A NP_001394910.1:p.Asp453Asn missense NM_001407982.1:c.1357G>A NP_001394911.1:p.Asp453Asn missense NM_001407983.1:c.1357G>A NP_001394912.1:p.Asp453Asn missense NM_001407984.1:c.1357G>A NP_001394913.1:p.Asp453Asn missense NM_001407985.1:c.1357G>A NP_001394914.1:p.Asp453Asn missense NM_001407986.1:c.1357G>A NP_001394915.1:p.Asp453Asn missense NM_001407990.1:c.1357G>A NP_001394919.1:p.Asp453Asn missense NM_001407991.1:c.1357G>A NP_001394920.1:p.Asp453Asn missense NM_001407992.1:c.1357G>A NP_001394921.1:p.Asp453Asn missense NM_001407993.1:c.1357G>A NP_001394922.1:p.Asp453Asn missense NM_001408392.1:c.1354G>A NP_001395321.1:p.Asp452Asn missense NM_001408396.1:c.1354G>A NP_001395325.1:p.Asp452Asn missense NM_001408397.1:c.1354G>A NP_001395326.1:p.Asp452Asn missense NM_001408398.1:c.1354G>A NP_001395327.1:p.Asp452Asn missense NM_001408399.1:c.1354G>A NP_001395328.1:p.Asp452Asn missense NM_001408400.1:c.1354G>A NP_001395329.1:p.Asp452Asn missense NM_001408401.1:c.1354G>A NP_001395330.1:p.Asp452Asn missense NM_001408402.1:c.1354G>A NP_001395331.1:p.Asp452Asn missense NM_001408403.1:c.1354G>A NP_001395332.1:p.Asp452Asn missense NM_001408404.1:c.1354G>A NP_001395333.1:p.Asp452Asn missense NM_001408406.1:c.1351G>A NP_001395335.1:p.Asp451Asn missense NM_001408407.1:c.1351G>A NP_001395336.1:p.Asp451Asn missense NM_001408408.1:c.1351G>A NP_001395337.1:p.Asp451Asn missense NM_001408409.1:c.1348G>A NP_001395338.1:p.Asp450Asn missense NM_001408410.1:c.1285G>A NP_001395339.1:p.Asp429Asn missense NM_001408411.1:c.1282G>A NP_001395340.1:p.Asp428Asn missense NM_001408412.1:c.1279G>A NP_001395341.1:p.Asp427Asn missense NM_001408413.1:c.1279G>A NP_001395342.1:p.Asp427Asn missense NM_001408414.1:c.1279G>A NP_001395343.1:p.Asp427Asn missense NM_001408415.1:c.1279G>A NP_001395344.1:p.Asp427Asn missense NM_001408416.1:c.1279G>A NP_001395345.1:p.Asp427Asn missense NM_001408418.1:c.1243G>A NP_001395347.1:p.Asp415Asn missense NM_001408419.1:c.1243G>A NP_001395348.1:p.Asp415Asn missense NM_001408420.1:c.1243G>A NP_001395349.1:p.Asp415Asn missense NM_001408421.1:c.1240G>A NP_001395350.1:p.Asp414Asn missense NM_001408422.1:c.1240G>A NP_001395351.1:p.Asp414Asn missense NM_001408423.1:c.1240G>A NP_001395352.1:p.Asp414Asn missense NM_001408424.1:c.1240G>A NP_001395353.1:p.Asp414Asn missense NM_001408425.1:c.1237G>A NP_001395354.1:p.Asp413Asn missense NM_001408426.1:c.1237G>A NP_001395355.1:p.Asp413Asn missense NM_001408427.1:c.1237G>A NP_001395356.1:p.Asp413Asn missense NM_001408428.1:c.1237G>A NP_001395357.1:p.Asp413Asn missense NM_001408429.1:c.1237G>A NP_001395358.1:p.Asp413Asn missense NM_001408430.1:c.1237G>A NP_001395359.1:p.Asp413Asn missense NM_001408431.1:c.1237G>A NP_001395360.1:p.Asp413Asn missense NM_001408432.1:c.1234G>A NP_001395361.1:p.Asp412Asn missense NM_001408433.1:c.1234G>A NP_001395362.1:p.Asp412Asn missense NM_001408434.1:c.1234G>A NP_001395363.1:p.Asp412Asn missense NM_001408435.1:c.1234G>A NP_001395364.1:p.Asp412Asn missense NM_001408436.1:c.1234G>A NP_001395365.1:p.Asp412Asn missense NM_001408437.1:c.1234G>A NP_001395366.1:p.Asp412Asn missense NM_001408438.1:c.1234G>A NP_001395367.1:p.Asp412Asn missense NM_001408439.1:c.1234G>A NP_001395368.1:p.Asp412Asn missense NM_001408440.1:c.1234G>A NP_001395369.1:p.Asp412Asn missense NM_001408441.1:c.1234G>A NP_001395370.1:p.Asp412Asn missense NM_001408442.1:c.1234G>A NP_001395371.1:p.Asp412Asn missense NM_001408443.1:c.1234G>A NP_001395372.1:p.Asp412Asn missense NM_001408444.1:c.1234G>A NP_001395373.1:p.Asp412Asn missense NM_001408445.1:c.1231G>A NP_001395374.1:p.Asp411Asn missense NM_001408446.1:c.1231G>A NP_001395375.1:p.Asp411Asn missense NM_001408447.1:c.1231G>A NP_001395376.1:p.Asp411Asn missense NM_001408448.1:c.1231G>A NP_001395377.1:p.Asp411Asn missense NM_001408450.1:c.1231G>A NP_001395379.1:p.Asp411Asn missense NM_001408451.1:c.1225G>A NP_001395380.1:p.Asp409Asn missense NM_001408452.1:c.1219G>A NP_001395381.1:p.Asp407Asn missense NM_001408453.1:c.1219G>A NP_001395382.1:p.Asp407Asn missense NM_001408454.1:c.1219G>A NP_001395383.1:p.Asp407Asn missense NM_001408455.1:c.1219G>A NP_001395384.1:p.Asp407Asn missense NM_001408456.1:c.1219G>A NP_001395385.1:p.Asp407Asn missense NM_001408457.1:c.1219G>A NP_001395386.1:p.Asp407Asn missense NM_001408458.1:c.1216G>A NP_001395387.1:p.Asp406Asn missense NM_001408459.1:c.1216G>A NP_001395388.1:p.Asp406Asn missense NM_001408460.1:c.1216G>A NP_001395389.1:p.Asp406Asn missense NM_001408461.1:c.1216G>A NP_001395390.1:p.Asp406Asn missense NM_001408462.1:c.1216G>A NP_001395391.1:p.Asp406Asn missense NM_001408463.1:c.1216G>A NP_001395392.1:p.Asp406Asn missense NM_001408464.1:c.1216G>A NP_001395393.1:p.Asp406Asn missense NM_001408465.1:c.1216G>A NP_001395394.1:p.Asp406Asn missense NM_001408466.1:c.1216G>A NP_001395395.1:p.Asp406Asn missense NM_001408467.1:c.1216G>A NP_001395396.1:p.Asp406Asn missense NM_001408468.1:c.1213G>A NP_001395397.1:p.Asp405Asn missense NM_001408469.1:c.1213G>A NP_001395398.1:p.Asp405Asn missense NM_001408470.1:c.1213G>A NP_001395399.1:p.Asp405Asn missense NM_001408472.1:c.1357G>A NP_001395401.1:p.Asp453Asn missense NM_001408473.1:c.1354G>A NP_001395402.1:p.Asp452Asn missense NM_001408474.1:c.1159G>A NP_001395403.1:p.Asp387Asn missense NM_001408475.1:c.1156G>A NP_001395404.1:p.Asp386Asn missense NM_001408476.1:c.1156G>A NP_001395405.1:p.Asp386Asn missense NM_001408478.1:c.1150G>A NP_001395407.1:p.Asp384Asn missense NM_001408479.1:c.1150G>A NP_001395408.1:p.Asp384Asn missense NM_001408480.1:c.1150G>A NP_001395409.1:p.Asp384Asn missense NM_001408481.1:c.1147G>A NP_001395410.1:p.Asp383Asn missense NM_001408482.1:c.1147G>A NP_001395411.1:p.Asp383Asn missense NM_001408483.1:c.1147G>A NP_001395412.1:p.Asp383Asn missense NM_001408484.1:c.1147G>A NP_001395413.1:p.Asp383Asn missense NM_001408485.1:c.1147G>A NP_001395414.1:p.Asp383Asn missense NM_001408489.1:c.1147G>A NP_001395418.1:p.Asp383Asn missense NM_001408490.1:c.1147G>A NP_001395419.1:p.Asp383Asn missense NM_001408491.1:c.1147G>A NP_001395420.1:p.Asp383Asn missense NM_001408492.1:c.1144G>A NP_001395421.1:p.Asp382Asn missense NM_001408493.1:c.1144G>A NP_001395422.1:p.Asp382Asn missense NM_001408494.1:c.1120G>A NP_001395423.1:p.Asp374Asn missense NM_001408495.1:c.1114G>A NP_001395424.1:p.Asp372Asn missense NM_001408496.1:c.1096G>A NP_001395425.1:p.Asp366Asn missense NM_001408497.1:c.1096G>A NP_001395426.1:p.Asp366Asn missense NM_001408498.1:c.1096G>A NP_001395427.1:p.Asp366Asn missense NM_001408499.1:c.1096G>A NP_001395428.1:p.Asp366Asn missense NM_001408500.1:c.1096G>A NP_001395429.1:p.Asp366Asn missense NM_001408501.1:c.1096G>A NP_001395430.1:p.Asp366Asn missense NM_001408502.1:c.1093G>A NP_001395431.1:p.Asp365Asn missense NM_001408503.1:c.1093G>A NP_001395432.1:p.Asp365Asn missense NM_001408504.1:c.1093G>A NP_001395433.1:p.Asp365Asn missense NM_001408505.1:c.1090G>A NP_001395434.1:p.Asp364Asn missense NM_001408506.1:c.1033G>A NP_001395435.1:p.Asp345Asn missense NM_001408507.1:c.1030G>A NP_001395436.1:p.Asp344Asn missense NM_001408508.1:c.1021G>A NP_001395437.1:p.Asp341Asn missense NM_001408509.1:c.1018G>A NP_001395438.1:p.Asp340Asn missense NM_001408510.1:c.979G>A NP_001395439.1:p.Asp327Asn missense NM_001408511.1:c.976G>A NP_001395440.1:p.Asp326Asn missense NM_001408512.1:c.856G>A NP_001395441.1:p.Asp286Asn missense NM_007297.4:c.4528G>A NP_009228.2:p.Asp1510Asn missense NM_007298.4:c.1357G>A NP_009229.2:p.Asp453Asn missense NM_007299.4:c.1357G>A NP_009230.2:p.Asp453Asn missense NM_007300.4:c.4732G>A NP_009231.2:p.Asp1578Asn missense NM_007304.2:c.1357G>A NP_009235.2:p.Asp453Asn missense NR_027676.2:n.4846G>A non-coding transcript variant NC_000017.11:g.43074337C>T NC_000017.10:g.41226354C>T NG_005905.2:g.143647G>A LRG_292:g.143647G>A LRG_292t1:c.4669G>A LRG_292p1:p.Asp1557Asn - Protein change
- D1557N, D453N, D1510N, D1578N, D1430N, D1444N, D1446N, D1468N, D1538N, D1553N, D1554N, D1556N, D1577N, D286N, D341N, D344N, D366N, D382N, D406N, D407N, D412N, D427N, D451N, D452N, D475N, D476N, D688N, D1260N, D1428N, D1445N, D1467N, D1485N, D1508N, D1509N, D1529N, D1537N, D1555N, D364N, D414N, D1261N, D1429N, D1469N, D1486N, D1488N, D1514N, D1515N, D1516N, D1531N, D1579N, D326N, D340N, D372N, D374N, D383N, D386N, D450N, D1388N, D1487N, D1490N, D1513N, D1530N, D1552N, D327N, D345N, D365N, D384N, D387N, D405N, D409N, D411N, D413N, D415N, D428N, D429N, D454N, D689N
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074336:C:T
-
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 |
13044 | 14850 | |
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
|
Nov 9, 2016 | RCV000510088.4 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jun 19, 2022 | RCV002527393.3 |
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
(Nov 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000608120.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The p.D1557N variant (also known as c.4669G>A), located in coding exon 13 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.D1557N variant (also known as c.4669G>A), located in coding exon 13 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4669. The aspartic acid at codon 1557 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jun 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003216695.2
First in ClinVar: Feb 07, 2023 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: 441446). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1557 of the BRCA1 protein (p.Asp1557Asn). (less)
|
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: 441446). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1557 of the BRCA1 protein (p.Asp1557Asn).
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:
The p.D1557N variant (also known as c.4669G>A), located in coding exon 13 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4669. The aspartic acid at codon 1557 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0003% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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: 441446). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1557 of the BRCA1 protein (p.Asp1557Asn).
Citations for germline classification of this variant
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Text-mined citations for rs80356906 ...
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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.