This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1843 of the BRCA1 protein (p.Ala1843Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496396). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5528C>T (p.Ala1843Val)
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.
(5)
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.
Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(2)
Uncertain significance(2); Likely benign(2)
5
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5528C>T (p.Ala1843Val)
Variation ID: 496396 Accession: VCV000496396.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045742 (GRCh38) [ NCBI UCSC ] 17: 41197759 (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 Mar 17, 2018 Sep 16, 2024 Jul 8, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5528C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1843Val missense NM_001407571.1:c.5315C>T NP_001394500.1:p.Ala1772Val missense NM_001407581.1:c.5594C>T NP_001394510.1:p.Ala1865Val missense NM_001407582.1:c.5594C>T NP_001394511.1:p.Ala1865Val missense NM_001407583.1:c.5591C>T NP_001394512.1:p.Ala1864Val missense NM_001407585.1:c.5591C>T NP_001394514.1:p.Ala1864Val missense NM_001407587.1:c.5591C>T NP_001394516.1:p.Ala1864Val missense NM_001407590.1:c.5588C>T NP_001394519.1:p.Ala1863Val missense NM_001407591.1:c.5588C>T NP_001394520.1:p.Ala1863Val missense NM_001407593.1:c.5528C>T NP_001394522.1:p.Ala1843Val missense NM_001407594.1:c.5528C>T NP_001394523.1:p.Ala1843Val missense NM_001407596.1:c.5528C>T NP_001394525.1:p.Ala1843Val missense NM_001407597.1:c.5528C>T NP_001394526.1:p.Ala1843Val missense NM_001407598.1:c.5528C>T NP_001394527.1:p.Ala1843Val missense NM_001407602.1:c.5528C>T NP_001394531.1:p.Ala1843Val missense NM_001407603.1:c.5528C>T NP_001394532.1:p.Ala1843Val missense NM_001407605.1:c.5528C>T NP_001394534.1:p.Ala1843Val missense NM_001407610.1:c.5525C>T NP_001394539.1:p.Ala1842Val missense NM_001407611.1:c.5525C>T NP_001394540.1:p.Ala1842Val missense NM_001407612.1:c.5525C>T NP_001394541.1:p.Ala1842Val missense NM_001407613.1:c.5525C>T NP_001394542.1:p.Ala1842Val missense NM_001407614.1:c.5525C>T NP_001394543.1:p.Ala1842Val missense NM_001407615.1:c.5525C>T NP_001394544.1:p.Ala1842Val missense NM_001407616.1:c.5525C>T NP_001394545.1:p.Ala1842Val missense NM_001407617.1:c.5525C>T NP_001394546.1:p.Ala1842Val missense NM_001407618.1:c.5525C>T NP_001394547.1:p.Ala1842Val missense NM_001407619.1:c.5525C>T NP_001394548.1:p.Ala1842Val missense NM_001407620.1:c.5525C>T NP_001394549.1:p.Ala1842Val missense NM_001407621.1:c.5525C>T NP_001394550.1:p.Ala1842Val missense NM_001407622.1:c.5525C>T NP_001394551.1:p.Ala1842Val missense NM_001407623.1:c.5525C>T NP_001394552.1:p.Ala1842Val missense NM_001407624.1:c.5525C>T NP_001394553.1:p.Ala1842Val missense NM_001407625.1:c.5525C>T NP_001394554.1:p.Ala1842Val missense NM_001407626.1:c.5525C>T NP_001394555.1:p.Ala1842Val missense NM_001407627.1:c.5522C>T NP_001394556.1:p.Ala1841Val missense NM_001407628.1:c.5522C>T NP_001394557.1:p.Ala1841Val missense NM_001407629.1:c.5522C>T NP_001394558.1:p.Ala1841Val missense NM_001407630.1:c.5522C>T NP_001394559.1:p.Ala1841Val missense NM_001407631.1:c.5522C>T NP_001394560.1:p.Ala1841Val missense NM_001407632.1:c.5522C>T NP_001394561.1:p.Ala1841Val missense NM_001407633.1:c.5522C>T NP_001394562.1:p.Ala1841Val missense NM_001407634.1:c.5522C>T NP_001394563.1:p.Ala1841Val missense NM_001407635.1:c.5522C>T NP_001394564.1:p.Ala1841Val missense NM_001407636.1:c.5522C>T NP_001394565.1:p.Ala1841Val missense NM_001407637.1:c.5522C>T NP_001394566.1:p.Ala1841Val missense NM_001407638.1:c.5522C>T NP_001394567.1:p.Ala1841Val missense NM_001407639.1:c.5522C>T NP_001394568.1:p.Ala1841Val missense NM_001407640.1:c.5522C>T NP_001394569.1:p.Ala1841Val missense NM_001407641.1:c.5522C>T NP_001394570.1:p.Ala1841Val missense NM_001407642.1:c.5522C>T NP_001394571.1:p.Ala1841Val missense NM_001407644.1:c.5519C>T NP_001394573.1:p.Ala1840Val missense NM_001407645.1:c.5519C>T NP_001394574.1:p.Ala1840Val missense NM_001407646.1:c.5516C>T NP_001394575.1:p.Ala1839Val missense NM_001407647.1:c.5513C>T NP_001394576.1:p.Ala1838Val missense NM_001407648.1:c.5471C>T NP_001394577.1:p.Ala1824Val missense NM_001407649.1:c.5468C>T NP_001394578.1:p.Ala1823Val missense NM_001407652.1:c.5450C>T NP_001394581.1:p.Ala1817Val missense NM_001407653.1:c.5450C>T NP_001394582.1:p.Ala1817Val missense NM_001407654.1:c.5450C>T NP_001394583.1:p.Ala1817Val missense NM_001407655.1:c.5450C>T NP_001394584.1:p.Ala1817Val missense NM_001407656.1:c.5447C>T NP_001394585.1:p.Ala1816Val missense NM_001407657.1:c.5447C>T NP_001394586.1:p.Ala1816Val missense NM_001407658.1:c.5447C>T NP_001394587.1:p.Ala1816Val missense NM_001407659.1:c.5444C>T NP_001394588.1:p.Ala1815Val missense NM_001407660.1:c.5444C>T NP_001394589.1:p.Ala1815Val missense NM_001407661.1:c.5444C>T NP_001394590.1:p.Ala1815Val missense NM_001407662.1:c.5444C>T NP_001394591.1:p.Ala1815Val missense NM_001407663.1:c.5444C>T NP_001394592.1:p.Ala1815Val missense NM_001407664.1:c.5405C>T NP_001394593.1:p.Ala1802Val missense NM_001407665.1:c.5405C>T NP_001394594.1:p.Ala1802Val missense NM_001407666.1:c.5405C>T NP_001394595.1:p.Ala1802Val missense NM_001407667.1:c.5405C>T NP_001394596.1:p.Ala1802Val missense NM_001407668.1:c.5405C>T NP_001394597.1:p.Ala1802Val missense NM_001407669.1:c.5405C>T NP_001394598.1:p.Ala1802Val missense NM_001407670.1:c.5402C>T NP_001394599.1:p.Ala1801Val missense NM_001407671.1:c.5402C>T NP_001394600.1:p.Ala1801Val missense NM_001407672.1:c.5402C>T NP_001394601.1:p.Ala1801Val missense NM_001407673.1:c.5402C>T NP_001394602.1:p.Ala1801Val missense NM_001407674.1:c.5402C>T NP_001394603.1:p.Ala1801Val missense NM_001407675.1:c.5402C>T NP_001394604.1:p.Ala1801Val missense NM_001407676.1:c.5402C>T NP_001394605.1:p.Ala1801Val missense NM_001407677.1:c.5402C>T NP_001394606.1:p.Ala1801Val missense NM_001407678.1:c.5402C>T NP_001394607.1:p.Ala1801Val missense NM_001407679.1:c.5402C>T NP_001394608.1:p.Ala1801Val missense NM_001407680.1:c.5402C>T NP_001394609.1:p.Ala1801Val missense NM_001407681.1:c.5399C>T NP_001394610.1:p.Ala1800Val missense NM_001407682.1:c.5399C>T NP_001394611.1:p.Ala1800Val missense NM_001407683.1:c.5399C>T NP_001394612.1:p.Ala1800Val missense NM_001407684.1:c.5399C>T NP_001394613.1:p.Ala1800Val missense NM_001407685.1:c.5399C>T NP_001394614.1:p.Ala1800Val missense NM_001407686.1:c.5399C>T NP_001394615.1:p.Ala1800Val missense NM_001407687.1:c.5399C>T NP_001394616.1:p.Ala1800Val missense NM_001407688.1:c.5399C>T NP_001394617.1:p.Ala1800Val missense NM_001407689.1:c.5399C>T NP_001394618.1:p.Ala1800Val missense NM_001407690.1:c.5396C>T NP_001394619.1:p.Ala1799Val missense NM_001407691.1:c.5396C>T NP_001394620.1:p.Ala1799Val missense NM_001407692.1:c.5387C>T NP_001394621.1:p.Ala1796Val missense NM_001407694.1:c.5387C>T NP_001394623.1:p.Ala1796Val missense NM_001407695.1:c.5387C>T NP_001394624.1:p.Ala1796Val missense NM_001407696.1:c.5387C>T NP_001394625.1:p.Ala1796Val missense NM_001407697.1:c.5387C>T NP_001394626.1:p.Ala1796Val missense NM_001407698.1:c.5387C>T NP_001394627.1:p.Ala1796Val missense NM_001407724.1:c.5387C>T NP_001394653.1:p.Ala1796Val missense NM_001407725.1:c.5387C>T NP_001394654.1:p.Ala1796Val missense NM_001407726.1:c.5387C>T NP_001394655.1:p.Ala1796Val missense NM_001407727.1:c.5387C>T NP_001394656.1:p.Ala1796Val missense NM_001407728.1:c.5387C>T NP_001394657.1:p.Ala1796Val missense NM_001407729.1:c.5387C>T NP_001394658.1:p.Ala1796Val missense NM_001407730.1:c.5387C>T NP_001394659.1:p.Ala1796Val missense NM_001407731.1:c.5387C>T NP_001394660.1:p.Ala1796Val missense NM_001407732.1:c.5384C>T NP_001394661.1:p.Ala1795Val missense NM_001407733.1:c.5384C>T NP_001394662.1:p.Ala1795Val missense NM_001407734.1:c.5384C>T NP_001394663.1:p.Ala1795Val missense NM_001407735.1:c.5384C>T NP_001394664.1:p.Ala1795Val missense NM_001407736.1:c.5384C>T NP_001394665.1:p.Ala1795Val missense NM_001407737.1:c.5384C>T NP_001394666.1:p.Ala1795Val missense NM_001407738.1:c.5384C>T NP_001394667.1:p.Ala1795Val missense NM_001407739.1:c.5384C>T NP_001394668.1:p.Ala1795Val missense NM_001407740.1:c.5384C>T NP_001394669.1:p.Ala1795Val missense NM_001407741.1:c.5384C>T NP_001394670.1:p.Ala1795Val missense NM_001407742.1:c.5384C>T NP_001394671.1:p.Ala1795Val missense NM_001407743.1:c.5384C>T NP_001394672.1:p.Ala1795Val missense NM_001407744.1:c.5384C>T NP_001394673.1:p.Ala1795Val missense NM_001407745.1:c.5384C>T NP_001394674.1:p.Ala1795Val missense NM_001407746.1:c.5384C>T NP_001394675.1:p.Ala1795Val missense NM_001407747.1:c.5384C>T NP_001394676.1:p.Ala1795Val missense NM_001407748.1:c.5384C>T NP_001394677.1:p.Ala1795Val missense NM_001407749.1:c.5384C>T NP_001394678.1:p.Ala1795Val missense NM_001407750.1:c.5384C>T NP_001394679.1:p.Ala1795Val missense NM_001407751.1:c.5384C>T NP_001394680.1:p.Ala1795Val missense NM_001407752.1:c.5384C>T NP_001394681.1:p.Ala1795Val missense NM_001407838.1:c.5381C>T NP_001394767.1:p.Ala1794Val missense NM_001407839.1:c.5381C>T NP_001394768.1:p.Ala1794Val missense NM_001407841.1:c.5381C>T NP_001394770.1:p.Ala1794Val missense NM_001407842.1:c.5381C>T NP_001394771.1:p.Ala1794Val missense NM_001407843.1:c.5381C>T NP_001394772.1:p.Ala1794Val missense NM_001407844.1:c.5381C>T NP_001394773.1:p.Ala1794Val missense NM_001407845.1:c.5381C>T NP_001394774.1:p.Ala1794Val missense NM_001407846.1:c.5381C>T NP_001394775.1:p.Ala1794Val missense NM_001407847.1:c.5381C>T NP_001394776.1:p.Ala1794Val missense NM_001407848.1:c.5381C>T NP_001394777.1:p.Ala1794Val missense NM_001407849.1:c.5381C>T NP_001394778.1:p.Ala1794Val missense NM_001407850.1:c.5381C>T NP_001394779.1:p.Ala1794Val missense NM_001407851.1:c.5381C>T NP_001394780.1:p.Ala1794Val missense NM_001407852.1:c.5381C>T NP_001394781.1:p.Ala1794Val missense NM_001407853.1:c.5381C>T NP_001394782.1:p.Ala1794Val missense NM_001407854.1:c.*42C>T NM_001407858.1:c.*42C>T NM_001407859.1:c.*42C>T NM_001407860.1:c.*42C>T NM_001407861.1:c.*42C>T NM_001407862.1:c.5327C>T NP_001394791.1:p.Ala1776Val missense NM_001407863.1:c.5324C>T NP_001394792.1:p.Ala1775Val missense NM_001407874.1:c.5321C>T NP_001394803.1:p.Ala1774Val missense NM_001407875.1:c.5321C>T NP_001394804.1:p.Ala1774Val missense NM_001407879.1:c.5318C>T NP_001394808.1:p.Ala1773Val missense NM_001407881.1:c.5318C>T NP_001394810.1:p.Ala1773Val missense NM_001407882.1:c.5318C>T NP_001394811.1:p.Ala1773Val missense NM_001407884.1:c.5318C>T NP_001394813.1:p.Ala1773Val missense NM_001407885.1:c.5318C>T NP_001394814.1:p.Ala1773Val missense NM_001407886.1:c.5318C>T NP_001394815.1:p.Ala1773Val missense NM_001407887.1:c.5318C>T NP_001394816.1:p.Ala1773Val missense NM_001407889.1:c.5318C>T NP_001394818.1:p.Ala1773Val missense NM_001407894.1:c.5315C>T NP_001394823.1:p.Ala1772Val missense NM_001407895.1:c.5315C>T NP_001394824.1:p.Ala1772Val missense NM_001407896.1:c.5315C>T NP_001394825.1:p.Ala1772Val missense NM_001407897.1:c.5315C>T NP_001394826.1:p.Ala1772Val missense NM_001407898.1:c.5315C>T NP_001394827.1:p.Ala1772Val missense NM_001407899.1:c.5315C>T NP_001394828.1:p.Ala1772Val missense NM_001407900.1:c.5315C>T NP_001394829.1:p.Ala1772Val missense NM_001407902.1:c.5315C>T NP_001394831.1:p.Ala1772Val missense NM_001407904.1:c.5315C>T NP_001394833.1:p.Ala1772Val missense NM_001407906.1:c.5315C>T NP_001394835.1:p.Ala1772Val missense NM_001407907.1:c.5315C>T NP_001394836.1:p.Ala1772Val missense NM_001407908.1:c.5315C>T NP_001394837.1:p.Ala1772Val missense NM_001407909.1:c.5315C>T NP_001394838.1:p.Ala1772Val missense NM_001407910.1:c.5315C>T NP_001394839.1:p.Ala1772Val missense NM_001407915.1:c.5312C>T NP_001394844.1:p.Ala1771Val missense NM_001407916.1:c.5312C>T NP_001394845.1:p.Ala1771Val missense NM_001407917.1:c.5312C>T NP_001394846.1:p.Ala1771Val missense NM_001407918.1:c.5312C>T NP_001394847.1:p.Ala1771Val missense NM_001407919.1:c.5276C>T NP_001394848.1:p.Ala1759Val missense NM_001407920.1:c.5264C>T NP_001394849.1:p.Ala1755Val missense NM_001407921.1:c.5264C>T NP_001394850.1:p.Ala1755Val missense NM_001407922.1:c.5264C>T NP_001394851.1:p.Ala1755Val missense NM_001407923.1:c.5264C>T NP_001394852.1:p.Ala1755Val missense NM_001407924.1:c.5264C>T NP_001394853.1:p.Ala1755Val missense NM_001407925.1:c.5264C>T NP_001394854.1:p.Ala1755Val missense NM_001407926.1:c.5264C>T NP_001394855.1:p.Ala1755Val missense NM_001407927.1:c.5261C>T NP_001394856.1:p.Ala1754Val missense NM_001407928.1:c.5261C>T NP_001394857.1:p.Ala1754Val missense NM_001407929.1:c.5261C>T NP_001394858.1:p.Ala1754Val missense NM_001407930.1:c.5261C>T NP_001394859.1:p.Ala1754Val missense NM_001407931.1:c.5261C>T NP_001394860.1:p.Ala1754Val missense NM_001407932.1:c.5261C>T NP_001394861.1:p.Ala1754Val missense NM_001407933.1:c.5261C>T NP_001394862.1:p.Ala1754Val missense NM_001407934.1:c.5258C>T NP_001394863.1:p.Ala1753Val missense NM_001407935.1:c.5258C>T NP_001394864.1:p.Ala1753Val missense NM_001407936.1:c.5258C>T NP_001394865.1:p.Ala1753Val missense NM_001407937.1:c.*42C>T NM_001407938.1:c.*42C>T NM_001407939.1:c.*42C>T NM_001407940.1:c.*42C>T NM_001407941.1:c.*42C>T NM_001407942.1:c.*42C>T NM_001407943.1:c.*42C>T NM_001407944.1:c.*42C>T NM_001407945.1:c.*42C>T NM_001407946.1:c.5195C>T NP_001394875.1:p.Ala1732Val missense NM_001407947.1:c.5195C>T NP_001394876.1:p.Ala1732Val missense NM_001407948.1:c.5195C>T NP_001394877.1:p.Ala1732Val missense NM_001407949.1:c.5195C>T NP_001394878.1:p.Ala1732Val missense NM_001407950.1:c.5192C>T NP_001394879.1:p.Ala1731Val missense NM_001407951.1:c.5192C>T NP_001394880.1:p.Ala1731Val missense NM_001407952.1:c.5192C>T NP_001394881.1:p.Ala1731Val missense NM_001407953.1:c.5192C>T NP_001394882.1:p.Ala1731Val missense NM_001407954.1:c.5192C>T NP_001394883.1:p.Ala1731Val missense NM_001407955.1:c.5192C>T NP_001394884.1:p.Ala1731Val missense NM_001407956.1:c.5189C>T NP_001394885.1:p.Ala1730Val missense NM_001407957.1:c.5189C>T NP_001394886.1:p.Ala1730Val missense NM_001407958.1:c.5189C>T NP_001394887.1:p.Ala1730Val missense NM_001407959.1:c.5147C>T NP_001394888.1:p.Ala1716Val missense NM_001407960.1:c.5144C>T NP_001394889.1:p.Ala1715Val missense NM_001407962.1:c.5144C>T NP_001394891.1:p.Ala1715Val missense NM_001407963.1:c.5141C>T NP_001394892.1:p.Ala1714Val missense NM_001407964.1:c.5066C>T NP_001394893.1:p.Ala1689Val missense NM_001407965.1:c.5021C>T NP_001394894.1:p.Ala1674Val missense NM_001407966.1:c.4640C>T NP_001394895.1:p.Ala1547Val missense NM_001407967.1:c.4637C>T NP_001394896.1:p.Ala1546Val missense NM_001407968.1:c.2924C>T NP_001394897.1:p.Ala975Val missense NM_001407969.1:c.2921C>T NP_001394898.1:p.Ala974Val missense NM_001407970.1:c.2285C>T NP_001394899.1:p.Ala762Val missense NM_001407971.1:c.2285C>T NP_001394900.1:p.Ala762Val missense NM_001407972.1:c.2282C>T NP_001394901.1:p.Ala761Val missense NM_001407973.1:c.2219C>T NP_001394902.1:p.Ala740Val missense NM_001407974.1:c.2219C>T NP_001394903.1:p.Ala740Val missense NM_001407975.1:c.2219C>T NP_001394904.1:p.Ala740Val missense NM_001407976.1:c.2219C>T NP_001394905.1:p.Ala740Val missense NM_001407977.1:c.2219C>T NP_001394906.1:p.Ala740Val missense NM_001407978.1:c.2219C>T NP_001394907.1:p.Ala740Val missense NM_001407979.1:c.2216C>T NP_001394908.1:p.Ala739Val missense NM_001407980.1:c.2216C>T NP_001394909.1:p.Ala739Val missense NM_001407981.1:c.2216C>T NP_001394910.1:p.Ala739Val missense NM_001407982.1:c.2216C>T NP_001394911.1:p.Ala739Val missense NM_001407983.1:c.2216C>T NP_001394912.1:p.Ala739Val missense NM_001407984.1:c.2216C>T NP_001394913.1:p.Ala739Val missense NM_001407985.1:c.2216C>T NP_001394914.1:p.Ala739Val missense NM_001407986.1:c.2216C>T NP_001394915.1:p.Ala739Val missense NM_001407990.1:c.2216C>T NP_001394919.1:p.Ala739Val missense NM_001407991.1:c.2216C>T NP_001394920.1:p.Ala739Val missense NM_001407992.1:c.2216C>T NP_001394921.1:p.Ala739Val missense NM_001407993.1:c.2216C>T NP_001394922.1:p.Ala739Val missense NM_001408392.1:c.2213C>T NP_001395321.1:p.Ala738Val missense NM_001408396.1:c.2213C>T NP_001395325.1:p.Ala738Val missense NM_001408397.1:c.2213C>T NP_001395326.1:p.Ala738Val missense NM_001408398.1:c.2213C>T NP_001395327.1:p.Ala738Val missense NM_001408399.1:c.2213C>T NP_001395328.1:p.Ala738Val missense NM_001408400.1:c.2213C>T NP_001395329.1:p.Ala738Val missense NM_001408401.1:c.2213C>T NP_001395330.1:p.Ala738Val missense NM_001408402.1:c.2213C>T NP_001395331.1:p.Ala738Val missense NM_001408403.1:c.2213C>T NP_001395332.1:p.Ala738Val missense NM_001408404.1:c.2213C>T NP_001395333.1:p.Ala738Val missense NM_001408406.1:c.2210C>T NP_001395335.1:p.Ala737Val missense NM_001408407.1:c.2210C>T NP_001395336.1:p.Ala737Val missense NM_001408408.1:c.2210C>T NP_001395337.1:p.Ala737Val missense NM_001408409.1:c.2207C>T NP_001395338.1:p.Ala736Val missense NM_001408410.1:c.2144C>T NP_001395339.1:p.Ala715Val missense NM_001408411.1:c.2141C>T NP_001395340.1:p.Ala714Val missense NM_001408412.1:c.2138C>T NP_001395341.1:p.Ala713Val missense NM_001408413.1:c.2138C>T NP_001395342.1:p.Ala713Val missense NM_001408414.1:c.2138C>T NP_001395343.1:p.Ala713Val missense NM_001408415.1:c.2138C>T NP_001395344.1:p.Ala713Val missense NM_001408416.1:c.2138C>T NP_001395345.1:p.Ala713Val missense NM_001408418.1:c.2102C>T NP_001395347.1:p.Ala701Val missense NM_001408419.1:c.2102C>T NP_001395348.1:p.Ala701Val missense NM_001408420.1:c.2102C>T NP_001395349.1:p.Ala701Val missense NM_001408421.1:c.2099C>T NP_001395350.1:p.Ala700Val missense NM_001408422.1:c.2099C>T NP_001395351.1:p.Ala700Val missense NM_001408423.1:c.2099C>T NP_001395352.1:p.Ala700Val missense NM_001408424.1:c.2099C>T NP_001395353.1:p.Ala700Val missense NM_001408425.1:c.2096C>T NP_001395354.1:p.Ala699Val missense NM_001408426.1:c.2096C>T NP_001395355.1:p.Ala699Val missense NM_001408427.1:c.2096C>T NP_001395356.1:p.Ala699Val missense NM_001408428.1:c.2096C>T NP_001395357.1:p.Ala699Val missense NM_001408429.1:c.2096C>T NP_001395358.1:p.Ala699Val missense NM_001408430.1:c.2096C>T NP_001395359.1:p.Ala699Val missense NM_001408431.1:c.2096C>T NP_001395360.1:p.Ala699Val missense NM_001408432.1:c.2093C>T NP_001395361.1:p.Ala698Val missense NM_001408433.1:c.2093C>T NP_001395362.1:p.Ala698Val missense NM_001408434.1:c.2093C>T NP_001395363.1:p.Ala698Val missense NM_001408435.1:c.2093C>T NP_001395364.1:p.Ala698Val missense NM_001408436.1:c.2093C>T NP_001395365.1:p.Ala698Val missense NM_001408437.1:c.2093C>T NP_001395366.1:p.Ala698Val missense NM_001408438.1:c.2093C>T NP_001395367.1:p.Ala698Val missense NM_001408439.1:c.2093C>T NP_001395368.1:p.Ala698Val missense NM_001408440.1:c.2093C>T NP_001395369.1:p.Ala698Val missense NM_001408441.1:c.2093C>T NP_001395370.1:p.Ala698Val missense NM_001408442.1:c.2093C>T NP_001395371.1:p.Ala698Val missense NM_001408443.1:c.2093C>T NP_001395372.1:p.Ala698Val missense NM_001408444.1:c.2093C>T NP_001395373.1:p.Ala698Val missense NM_001408445.1:c.2090C>T NP_001395374.1:p.Ala697Val missense NM_001408446.1:c.2090C>T NP_001395375.1:p.Ala697Val missense NM_001408447.1:c.2090C>T NP_001395376.1:p.Ala697Val missense NM_001408448.1:c.2090C>T NP_001395377.1:p.Ala697Val missense NM_001408450.1:c.2090C>T NP_001395379.1:p.Ala697Val missense NM_001408451.1:c.2084C>T NP_001395380.1:p.Ala695Val missense NM_001408452.1:c.2078C>T NP_001395381.1:p.Ala693Val missense NM_001408453.1:c.2078C>T NP_001395382.1:p.Ala693Val missense NM_001408454.1:c.2078C>T NP_001395383.1:p.Ala693Val missense NM_001408455.1:c.2078C>T NP_001395384.1:p.Ala693Val missense NM_001408456.1:c.2078C>T NP_001395385.1:p.Ala693Val missense NM_001408457.1:c.2078C>T NP_001395386.1:p.Ala693Val missense NM_001408458.1:c.2075C>T NP_001395387.1:p.Ala692Val missense NM_001408459.1:c.2075C>T NP_001395388.1:p.Ala692Val missense NM_001408460.1:c.2075C>T NP_001395389.1:p.Ala692Val missense NM_001408461.1:c.2075C>T NP_001395390.1:p.Ala692Val missense NM_001408462.1:c.2075C>T NP_001395391.1:p.Ala692Val missense NM_001408463.1:c.2075C>T NP_001395392.1:p.Ala692Val missense NM_001408464.1:c.2075C>T NP_001395393.1:p.Ala692Val missense NM_001408465.1:c.2075C>T NP_001395394.1:p.Ala692Val missense NM_001408466.1:c.2075C>T NP_001395395.1:p.Ala692Val missense NM_001408467.1:c.2075C>T NP_001395396.1:p.Ala692Val missense NM_001408468.1:c.2072C>T NP_001395397.1:p.Ala691Val missense NM_001408469.1:c.2072C>T NP_001395398.1:p.Ala691Val missense NM_001408470.1:c.2072C>T NP_001395399.1:p.Ala691Val missense NM_001408472.1:c.*42C>T NM_001408473.1:c.*42C>T NM_001408474.1:c.2018C>T NP_001395403.1:p.Ala673Val missense NM_001408475.1:c.2015C>T NP_001395404.1:p.Ala672Val missense NM_001408476.1:c.2015C>T NP_001395405.1:p.Ala672Val missense NM_001408478.1:c.2009C>T NP_001395407.1:p.Ala670Val missense NM_001408479.1:c.2009C>T NP_001395408.1:p.Ala670Val missense NM_001408480.1:c.2009C>T NP_001395409.1:p.Ala670Val missense NM_001408481.1:c.2006C>T NP_001395410.1:p.Ala669Val missense NM_001408482.1:c.2006C>T NP_001395411.1:p.Ala669Val missense NM_001408483.1:c.2006C>T NP_001395412.1:p.Ala669Val missense NM_001408484.1:c.2006C>T NP_001395413.1:p.Ala669Val missense NM_001408485.1:c.2006C>T NP_001395414.1:p.Ala669Val missense NM_001408489.1:c.2006C>T NP_001395418.1:p.Ala669Val missense NM_001408490.1:c.2006C>T NP_001395419.1:p.Ala669Val missense NM_001408491.1:c.2006C>T NP_001395420.1:p.Ala669Val missense NM_001408492.1:c.2003C>T NP_001395421.1:p.Ala668Val missense NM_001408493.1:c.2003C>T NP_001395422.1:p.Ala668Val missense NM_001408494.1:c.1979C>T NP_001395423.1:p.Ala660Val missense NM_001408495.1:c.1973C>T NP_001395424.1:p.Ala658Val missense NM_001408496.1:c.1955C>T NP_001395425.1:p.Ala652Val missense NM_001408497.1:c.1955C>T NP_001395426.1:p.Ala652Val missense NM_001408498.1:c.1955C>T NP_001395427.1:p.Ala652Val missense NM_001408499.1:c.1955C>T NP_001395428.1:p.Ala652Val missense NM_001408500.1:c.1955C>T NP_001395429.1:p.Ala652Val missense NM_001408501.1:c.1955C>T NP_001395430.1:p.Ala652Val missense NM_001408502.1:c.1952C>T NP_001395431.1:p.Ala651Val missense NM_001408503.1:c.1952C>T NP_001395432.1:p.Ala651Val missense NM_001408504.1:c.1952C>T NP_001395433.1:p.Ala651Val missense NM_001408505.1:c.1949C>T NP_001395434.1:p.Ala650Val missense NM_001408506.1:c.1892C>T NP_001395435.1:p.Ala631Val missense NM_001408507.1:c.1889C>T NP_001395436.1:p.Ala630Val missense NM_001408508.1:c.1880C>T NP_001395437.1:p.Ala627Val missense NM_001408509.1:c.1877C>T NP_001395438.1:p.Ala626Val missense NM_001408510.1:c.1838C>T NP_001395439.1:p.Ala613Val missense NM_001408511.1:c.1835C>T NP_001395440.1:p.Ala612Val missense NM_001408512.1:c.1715C>T NP_001395441.1:p.Ala572Val missense NM_001408513.1:c.1688C>T NP_001395442.1:p.Ala563Val missense NM_001408514.1:c.1292C>T NP_001395443.1:p.Ala431Val missense NM_007297.4:c.5387C>T NP_009228.2:p.Ala1796Val missense NM_007298.4:c.2216C>T NP_009229.2:p.Ala739Val missense NM_007299.4:c.*42C>T 3 prime UTR NM_007300.4:c.5591C>T NP_009231.2:p.Ala1864Val missense NM_007304.2:c.2216C>T NP_009235.2:p.Ala739Val missense NR_027676.2:n.5705C>T non-coding transcript variant NC_000017.11:g.43045742G>A NC_000017.10:g.41197759G>A NG_005905.2:g.172242C>T LRG_292:g.172242C>T LRG_292t1:c.5528C>T LRG_292p1:p.Ala1843Val - Protein change
- A1843V, A1864V, A739V, A1796V, A1546V, A1674V, A1714V, A1772V, A1799V, A1801V, A1823V, A1824V, A1839V, A1863V, A1865V, A563V, A572V, A650V, A658V, A660V, A693V, A695V, A697V, A700V, A737V, A974V, A1547V, A1731V, A1753V, A1771V, A1776V, A1795V, A1800V, A1817V, A1838V, A1842V, A431V, A612V, A651V, A652V, A670V, A672V, A691V, A713V, A740V, A975V, A1716V, A1732V, A1754V, A1755V, A1773V, A1775V, A1794V, A1802V, A1815V, A1816V, A1840V, A1841V, A630V, A631V, A692V, A698V, A715V, A761V, A762V, A1689V, A1715V, A1730V, A1759V, A1774V, A613V, A626V, A627V, A668V, A669V, A673V, A699V, A701V, A714V, A736V, A738V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43045741:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functionally_normal; Sequence Ontology [ SO:0002219]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5528C>T, a MISSENSE variant, produced a function score of -0.38, corresponding to a functional classification of FUNCTIONAL. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
- 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
|
Oct 18, 2023 | RCV000691407.11 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 16, 2021 | RCV001024228.4 | |
| Uncertain significance (2) |
criteria provided, single submitter
|
Sep 28, 2023 | RCV001076359.4 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jul 8, 2024 | RCV004701679.1 |
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
(Sep 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212749.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Uncertain significance
(Oct 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000819185.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1843 of the BRCA1 protein (p.Ala1843Val). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1843 of the BRCA1 protein (p.Ala1843Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496396). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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. (less)
|
|
|
Likely benign
(Apr 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001186210.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Likely benign
(Jul 08, 2024)
|
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: SCV000699261.2
First in ClinVar: Mar 17, 2018 Last updated: Sep 16, 2024 |
Comment:
Variant summary: BRCA1 c.5528C>T (p.Ala1843Val) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of … (more)
Variant summary: BRCA1 c.5528C>T (p.Ala1843Val) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251346 control chromosomes. 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.5528C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. At least one functional study reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The following publication has been ascertained in the context of this evaluation (PMID: 30209399). ClinVar contains an entry for this variant (Variation ID: 496396). Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001242092.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.377550923552376
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Comment:
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Variant summary: BRCA1 c.5528C>T (p.Ala1843Val) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251346 control chromosomes. 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.5528C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. At least one functional study reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The following publication has been ascertained in the context of this evaluation (PMID: 30209399). ClinVar contains an entry for this variant (Variation ID: 496396). Based on the evidence outlined above, the variant was classified as likely benign.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
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
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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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functionally_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001242092.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5528C>T, a MISSENSE variant, produced a function score of -0.38, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5528C>T, a MISSENSE variant, produced a function score of -0.38, corresponding to a functional classification of FUNCTIONAL. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1843 of the BRCA1 protein (p.Ala1843Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496396). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Variant summary: BRCA1 c.5528C>T (p.Ala1843Val) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251346 control chromosomes. 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.5528C>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. At least one functional study reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The following publication has been ascertained in the context of this evaluation (PMID: 30209399). ClinVar contains an entry for this variant (Variation ID: 496396). Based on the evidence outlined above, the variant was classified as likely benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs730881447 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 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.