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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) 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: 868637). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs397509295, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 1847 of the BRCA1 protein (p.Cys1847Trp).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5541C>G (p.Cys1847Trp)
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, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5541C>G (p.Cys1847Trp)
Variation ID: 868637 Accession: VCV000868637.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045729 (GRCh38) [ NCBI UCSC ] 17: 41197746 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 18, 2020 Feb 20, 2024 Sep 10, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5541C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Cys1847Trp missense NM_001407571.1:c.5328C>G NP_001394500.1:p.Cys1776Trp missense NM_001407581.1:c.5607C>G NP_001394510.1:p.Cys1869Trp missense NM_001407582.1:c.5607C>G NP_001394511.1:p.Cys1869Trp missense NM_001407583.1:c.5604C>G NP_001394512.1:p.Cys1868Trp missense NM_001407585.1:c.5604C>G NP_001394514.1:p.Cys1868Trp missense NM_001407587.1:c.5604C>G NP_001394516.1:p.Cys1868Trp missense NM_001407590.1:c.5601C>G NP_001394519.1:p.Cys1867Trp missense NM_001407591.1:c.5601C>G NP_001394520.1:p.Cys1867Trp missense NM_001407593.1:c.5541C>G NP_001394522.1:p.Cys1847Trp missense NM_001407594.1:c.5541C>G NP_001394523.1:p.Cys1847Trp missense NM_001407596.1:c.5541C>G NP_001394525.1:p.Cys1847Trp missense NM_001407597.1:c.5541C>G NP_001394526.1:p.Cys1847Trp missense NM_001407598.1:c.5541C>G NP_001394527.1:p.Cys1847Trp missense NM_001407602.1:c.5541C>G NP_001394531.1:p.Cys1847Trp missense NM_001407603.1:c.5541C>G NP_001394532.1:p.Cys1847Trp missense NM_001407605.1:c.5541C>G NP_001394534.1:p.Cys1847Trp missense NM_001407610.1:c.5538C>G NP_001394539.1:p.Cys1846Trp missense NM_001407611.1:c.5538C>G NP_001394540.1:p.Cys1846Trp missense NM_001407612.1:c.5538C>G NP_001394541.1:p.Cys1846Trp missense NM_001407613.1:c.5538C>G NP_001394542.1:p.Cys1846Trp missense NM_001407614.1:c.5538C>G NP_001394543.1:p.Cys1846Trp missense NM_001407615.1:c.5538C>G NP_001394544.1:p.Cys1846Trp missense NM_001407616.1:c.5538C>G NP_001394545.1:p.Cys1846Trp missense NM_001407617.1:c.5538C>G NP_001394546.1:p.Cys1846Trp missense NM_001407618.1:c.5538C>G NP_001394547.1:p.Cys1846Trp missense NM_001407619.1:c.5538C>G NP_001394548.1:p.Cys1846Trp missense NM_001407620.1:c.5538C>G NP_001394549.1:p.Cys1846Trp missense NM_001407621.1:c.5538C>G NP_001394550.1:p.Cys1846Trp missense NM_001407622.1:c.5538C>G NP_001394551.1:p.Cys1846Trp missense NM_001407623.1:c.5538C>G NP_001394552.1:p.Cys1846Trp missense NM_001407624.1:c.5538C>G NP_001394553.1:p.Cys1846Trp missense NM_001407625.1:c.5538C>G NP_001394554.1:p.Cys1846Trp missense NM_001407626.1:c.5538C>G NP_001394555.1:p.Cys1846Trp missense NM_001407627.1:c.5535C>G NP_001394556.1:p.Cys1845Trp missense NM_001407628.1:c.5535C>G NP_001394557.1:p.Cys1845Trp missense NM_001407629.1:c.5535C>G NP_001394558.1:p.Cys1845Trp missense NM_001407630.1:c.5535C>G NP_001394559.1:p.Cys1845Trp missense NM_001407631.1:c.5535C>G NP_001394560.1:p.Cys1845Trp missense NM_001407632.1:c.5535C>G NP_001394561.1:p.Cys1845Trp missense NM_001407633.1:c.5535C>G NP_001394562.1:p.Cys1845Trp missense NM_001407634.1:c.5535C>G NP_001394563.1:p.Cys1845Trp missense NM_001407635.1:c.5535C>G NP_001394564.1:p.Cys1845Trp missense NM_001407636.1:c.5535C>G NP_001394565.1:p.Cys1845Trp missense NM_001407637.1:c.5535C>G NP_001394566.1:p.Cys1845Trp missense NM_001407638.1:c.5535C>G NP_001394567.1:p.Cys1845Trp missense NM_001407639.1:c.5535C>G NP_001394568.1:p.Cys1845Trp missense NM_001407640.1:c.5535C>G NP_001394569.1:p.Cys1845Trp missense NM_001407641.1:c.5535C>G NP_001394570.1:p.Cys1845Trp missense NM_001407642.1:c.5535C>G NP_001394571.1:p.Cys1845Trp missense NM_001407644.1:c.5532C>G NP_001394573.1:p.Cys1844Trp missense NM_001407645.1:c.5532C>G NP_001394574.1:p.Cys1844Trp missense NM_001407646.1:c.5529C>G NP_001394575.1:p.Cys1843Trp missense NM_001407647.1:c.5526C>G NP_001394576.1:p.Cys1842Trp missense NM_001407648.1:c.5484C>G NP_001394577.1:p.Cys1828Trp missense NM_001407649.1:c.5481C>G NP_001394578.1:p.Cys1827Trp missense NM_001407652.1:c.5463C>G NP_001394581.1:p.Cys1821Trp missense NM_001407653.1:c.5463C>G NP_001394582.1:p.Cys1821Trp missense NM_001407654.1:c.5463C>G NP_001394583.1:p.Cys1821Trp missense NM_001407655.1:c.5463C>G NP_001394584.1:p.Cys1821Trp missense NM_001407656.1:c.5460C>G NP_001394585.1:p.Cys1820Trp missense NM_001407657.1:c.5460C>G NP_001394586.1:p.Cys1820Trp missense NM_001407658.1:c.5460C>G NP_001394587.1:p.Cys1820Trp missense NM_001407659.1:c.5457C>G NP_001394588.1:p.Cys1819Trp missense NM_001407660.1:c.5457C>G NP_001394589.1:p.Cys1819Trp missense NM_001407661.1:c.5457C>G NP_001394590.1:p.Cys1819Trp missense NM_001407662.1:c.5457C>G NP_001394591.1:p.Cys1819Trp missense NM_001407663.1:c.5457C>G NP_001394592.1:p.Cys1819Trp missense NM_001407664.1:c.5418C>G NP_001394593.1:p.Cys1806Trp missense NM_001407665.1:c.5418C>G NP_001394594.1:p.Cys1806Trp missense NM_001407666.1:c.5418C>G NP_001394595.1:p.Cys1806Trp missense NM_001407667.1:c.5418C>G NP_001394596.1:p.Cys1806Trp missense NM_001407668.1:c.5418C>G NP_001394597.1:p.Cys1806Trp missense NM_001407669.1:c.5418C>G NP_001394598.1:p.Cys1806Trp missense NM_001407670.1:c.5415C>G NP_001394599.1:p.Cys1805Trp missense NM_001407671.1:c.5415C>G NP_001394600.1:p.Cys1805Trp missense NM_001407672.1:c.5415C>G NP_001394601.1:p.Cys1805Trp missense NM_001407673.1:c.5415C>G NP_001394602.1:p.Cys1805Trp missense NM_001407674.1:c.5415C>G NP_001394603.1:p.Cys1805Trp missense NM_001407675.1:c.5415C>G NP_001394604.1:p.Cys1805Trp missense NM_001407676.1:c.5415C>G NP_001394605.1:p.Cys1805Trp missense NM_001407677.1:c.5415C>G NP_001394606.1:p.Cys1805Trp missense NM_001407678.1:c.5415C>G NP_001394607.1:p.Cys1805Trp missense NM_001407679.1:c.5415C>G NP_001394608.1:p.Cys1805Trp missense NM_001407680.1:c.5415C>G NP_001394609.1:p.Cys1805Trp missense NM_001407681.1:c.5412C>G NP_001394610.1:p.Cys1804Trp missense NM_001407682.1:c.5412C>G NP_001394611.1:p.Cys1804Trp missense NM_001407683.1:c.5412C>G NP_001394612.1:p.Cys1804Trp missense NM_001407684.1:c.5412C>G NP_001394613.1:p.Cys1804Trp missense NM_001407685.1:c.5412C>G NP_001394614.1:p.Cys1804Trp missense NM_001407686.1:c.5412C>G NP_001394615.1:p.Cys1804Trp missense NM_001407687.1:c.5412C>G NP_001394616.1:p.Cys1804Trp missense NM_001407688.1:c.5412C>G NP_001394617.1:p.Cys1804Trp missense NM_001407689.1:c.5412C>G NP_001394618.1:p.Cys1804Trp missense NM_001407690.1:c.5409C>G NP_001394619.1:p.Cys1803Trp missense NM_001407691.1:c.5409C>G NP_001394620.1:p.Cys1803Trp missense NM_001407692.1:c.5400C>G NP_001394621.1:p.Cys1800Trp missense NM_001407694.1:c.5400C>G NP_001394623.1:p.Cys1800Trp missense NM_001407695.1:c.5400C>G NP_001394624.1:p.Cys1800Trp missense NM_001407696.1:c.5400C>G NP_001394625.1:p.Cys1800Trp missense NM_001407697.1:c.5400C>G NP_001394626.1:p.Cys1800Trp missense NM_001407698.1:c.5400C>G NP_001394627.1:p.Cys1800Trp missense NM_001407724.1:c.5400C>G NP_001394653.1:p.Cys1800Trp missense NM_001407725.1:c.5400C>G NP_001394654.1:p.Cys1800Trp missense NM_001407726.1:c.5400C>G NP_001394655.1:p.Cys1800Trp missense NM_001407727.1:c.5400C>G NP_001394656.1:p.Cys1800Trp missense NM_001407728.1:c.5400C>G NP_001394657.1:p.Cys1800Trp missense NM_001407729.1:c.5400C>G NP_001394658.1:p.Cys1800Trp missense NM_001407730.1:c.5400C>G NP_001394659.1:p.Cys1800Trp missense NM_001407731.1:c.5400C>G NP_001394660.1:p.Cys1800Trp missense NM_001407732.1:c.5397C>G NP_001394661.1:p.Cys1799Trp missense NM_001407733.1:c.5397C>G NP_001394662.1:p.Cys1799Trp missense NM_001407734.1:c.5397C>G NP_001394663.1:p.Cys1799Trp missense NM_001407735.1:c.5397C>G NP_001394664.1:p.Cys1799Trp missense NM_001407736.1:c.5397C>G NP_001394665.1:p.Cys1799Trp missense NM_001407737.1:c.5397C>G NP_001394666.1:p.Cys1799Trp missense NM_001407738.1:c.5397C>G NP_001394667.1:p.Cys1799Trp missense NM_001407739.1:c.5397C>G NP_001394668.1:p.Cys1799Trp missense NM_001407740.1:c.5397C>G NP_001394669.1:p.Cys1799Trp missense NM_001407741.1:c.5397C>G NP_001394670.1:p.Cys1799Trp missense NM_001407742.1:c.5397C>G NP_001394671.1:p.Cys1799Trp missense NM_001407743.1:c.5397C>G NP_001394672.1:p.Cys1799Trp missense NM_001407744.1:c.5397C>G NP_001394673.1:p.Cys1799Trp missense NM_001407745.1:c.5397C>G NP_001394674.1:p.Cys1799Trp missense NM_001407746.1:c.5397C>G NP_001394675.1:p.Cys1799Trp missense NM_001407747.1:c.5397C>G NP_001394676.1:p.Cys1799Trp missense NM_001407748.1:c.5397C>G NP_001394677.1:p.Cys1799Trp missense NM_001407749.1:c.5397C>G NP_001394678.1:p.Cys1799Trp missense NM_001407750.1:c.5397C>G NP_001394679.1:p.Cys1799Trp missense NM_001407751.1:c.5397C>G NP_001394680.1:p.Cys1799Trp missense NM_001407752.1:c.5397C>G NP_001394681.1:p.Cys1799Trp missense NM_001407838.1:c.5394C>G NP_001394767.1:p.Cys1798Trp missense NM_001407839.1:c.5394C>G NP_001394768.1:p.Cys1798Trp missense NM_001407841.1:c.5394C>G NP_001394770.1:p.Cys1798Trp missense NM_001407842.1:c.5394C>G NP_001394771.1:p.Cys1798Trp missense NM_001407843.1:c.5394C>G NP_001394772.1:p.Cys1798Trp missense NM_001407844.1:c.5394C>G NP_001394773.1:p.Cys1798Trp missense NM_001407845.1:c.5394C>G NP_001394774.1:p.Cys1798Trp missense NM_001407846.1:c.5394C>G NP_001394775.1:p.Cys1798Trp missense NM_001407847.1:c.5394C>G NP_001394776.1:p.Cys1798Trp missense NM_001407848.1:c.5394C>G NP_001394777.1:p.Cys1798Trp missense NM_001407849.1:c.5394C>G NP_001394778.1:p.Cys1798Trp missense NM_001407850.1:c.5394C>G NP_001394779.1:p.Cys1798Trp missense NM_001407851.1:c.5394C>G NP_001394780.1:p.Cys1798Trp missense NM_001407852.1:c.5394C>G NP_001394781.1:p.Cys1798Trp missense NM_001407853.1:c.5394C>G NP_001394782.1:p.Cys1798Trp missense NM_001407854.1:c.*55C>G NM_001407858.1:c.*55C>G NM_001407859.1:c.*55C>G NM_001407860.1:c.*55C>G NM_001407861.1:c.*55C>G NM_001407862.1:c.5340C>G NP_001394791.1:p.Cys1780Trp missense NM_001407863.1:c.5337C>G NP_001394792.1:p.Cys1779Trp missense NM_001407874.1:c.5334C>G NP_001394803.1:p.Cys1778Trp missense NM_001407875.1:c.5334C>G NP_001394804.1:p.Cys1778Trp missense NM_001407879.1:c.5331C>G NP_001394808.1:p.Cys1777Trp missense NM_001407881.1:c.5331C>G NP_001394810.1:p.Cys1777Trp missense NM_001407882.1:c.5331C>G NP_001394811.1:p.Cys1777Trp missense NM_001407884.1:c.5331C>G NP_001394813.1:p.Cys1777Trp missense NM_001407885.1:c.5331C>G NP_001394814.1:p.Cys1777Trp missense NM_001407886.1:c.5331C>G NP_001394815.1:p.Cys1777Trp missense NM_001407887.1:c.5331C>G NP_001394816.1:p.Cys1777Trp missense NM_001407889.1:c.5331C>G NP_001394818.1:p.Cys1777Trp missense NM_001407894.1:c.5328C>G NP_001394823.1:p.Cys1776Trp missense NM_001407895.1:c.5328C>G NP_001394824.1:p.Cys1776Trp missense NM_001407896.1:c.5328C>G NP_001394825.1:p.Cys1776Trp missense NM_001407897.1:c.5328C>G NP_001394826.1:p.Cys1776Trp missense NM_001407898.1:c.5328C>G NP_001394827.1:p.Cys1776Trp missense NM_001407899.1:c.5328C>G NP_001394828.1:p.Cys1776Trp missense NM_001407900.1:c.5328C>G NP_001394829.1:p.Cys1776Trp missense NM_001407902.1:c.5328C>G NP_001394831.1:p.Cys1776Trp missense NM_001407904.1:c.5328C>G NP_001394833.1:p.Cys1776Trp missense NM_001407906.1:c.5328C>G NP_001394835.1:p.Cys1776Trp missense NM_001407907.1:c.5328C>G NP_001394836.1:p.Cys1776Trp missense NM_001407908.1:c.5328C>G NP_001394837.1:p.Cys1776Trp missense NM_001407909.1:c.5328C>G NP_001394838.1:p.Cys1776Trp missense NM_001407910.1:c.5328C>G NP_001394839.1:p.Cys1776Trp missense NM_001407915.1:c.5325C>G NP_001394844.1:p.Cys1775Trp missense NM_001407916.1:c.5325C>G NP_001394845.1:p.Cys1775Trp missense NM_001407917.1:c.5325C>G NP_001394846.1:p.Cys1775Trp missense NM_001407918.1:c.5325C>G NP_001394847.1:p.Cys1775Trp missense NM_001407919.1:c.5289C>G NP_001394848.1:p.Cys1763Trp missense NM_001407920.1:c.5277C>G NP_001394849.1:p.Cys1759Trp missense NM_001407921.1:c.5277C>G NP_001394850.1:p.Cys1759Trp missense NM_001407922.1:c.5277C>G NP_001394851.1:p.Cys1759Trp missense NM_001407923.1:c.5277C>G NP_001394852.1:p.Cys1759Trp missense NM_001407924.1:c.5277C>G NP_001394853.1:p.Cys1759Trp missense NM_001407925.1:c.5277C>G NP_001394854.1:p.Cys1759Trp missense NM_001407926.1:c.5277C>G NP_001394855.1:p.Cys1759Trp missense NM_001407927.1:c.5274C>G NP_001394856.1:p.Cys1758Trp missense NM_001407928.1:c.5274C>G NP_001394857.1:p.Cys1758Trp missense NM_001407929.1:c.5274C>G NP_001394858.1:p.Cys1758Trp missense NM_001407930.1:c.5274C>G NP_001394859.1:p.Cys1758Trp missense NM_001407931.1:c.5274C>G NP_001394860.1:p.Cys1758Trp missense NM_001407932.1:c.5274C>G NP_001394861.1:p.Cys1758Trp missense NM_001407933.1:c.5274C>G NP_001394862.1:p.Cys1758Trp missense NM_001407934.1:c.5271C>G NP_001394863.1:p.Cys1757Trp missense NM_001407935.1:c.5271C>G NP_001394864.1:p.Cys1757Trp missense NM_001407936.1:c.5271C>G NP_001394865.1:p.Cys1757Trp missense NM_001407937.1:c.*55C>G NM_001407938.1:c.*55C>G NM_001407939.1:c.*55C>G NM_001407940.1:c.*55C>G NM_001407941.1:c.*55C>G NM_001407942.1:c.*55C>G NM_001407943.1:c.*55C>G NM_001407944.1:c.*55C>G NM_001407945.1:c.*55C>G NM_001407946.1:c.5208C>G NP_001394875.1:p.Cys1736Trp missense NM_001407947.1:c.5208C>G NP_001394876.1:p.Cys1736Trp missense NM_001407948.1:c.5208C>G NP_001394877.1:p.Cys1736Trp missense NM_001407949.1:c.5208C>G NP_001394878.1:p.Cys1736Trp missense NM_001407950.1:c.5205C>G NP_001394879.1:p.Cys1735Trp missense NM_001407951.1:c.5205C>G NP_001394880.1:p.Cys1735Trp missense NM_001407952.1:c.5205C>G NP_001394881.1:p.Cys1735Trp missense NM_001407953.1:c.5205C>G NP_001394882.1:p.Cys1735Trp missense NM_001407954.1:c.5205C>G NP_001394883.1:p.Cys1735Trp missense NM_001407955.1:c.5205C>G NP_001394884.1:p.Cys1735Trp missense NM_001407956.1:c.5202C>G NP_001394885.1:p.Cys1734Trp missense NM_001407957.1:c.5202C>G NP_001394886.1:p.Cys1734Trp missense NM_001407958.1:c.5202C>G NP_001394887.1:p.Cys1734Trp missense NM_001407959.1:c.5160C>G NP_001394888.1:p.Cys1720Trp missense NM_001407960.1:c.5157C>G NP_001394889.1:p.Cys1719Trp missense NM_001407962.1:c.5157C>G NP_001394891.1:p.Cys1719Trp missense NM_001407963.1:c.5154C>G NP_001394892.1:p.Cys1718Trp missense NM_001407964.1:c.5079C>G NP_001394893.1:p.Cys1693Trp missense NM_001407965.1:c.5034C>G NP_001394894.1:p.Cys1678Trp missense NM_001407966.1:c.4653C>G NP_001394895.1:p.Cys1551Trp missense NM_001407967.1:c.4650C>G NP_001394896.1:p.Cys1550Trp missense NM_001407968.1:c.2937C>G NP_001394897.1:p.Cys979Trp missense NM_001407969.1:c.2934C>G NP_001394898.1:p.Cys978Trp missense NM_001407970.1:c.2298C>G NP_001394899.1:p.Cys766Trp missense NM_001407971.1:c.2298C>G NP_001394900.1:p.Cys766Trp missense NM_001407972.1:c.2295C>G NP_001394901.1:p.Cys765Trp missense NM_001407973.1:c.2232C>G NP_001394902.1:p.Cys744Trp missense NM_001407974.1:c.2232C>G NP_001394903.1:p.Cys744Trp missense NM_001407975.1:c.2232C>G NP_001394904.1:p.Cys744Trp missense NM_001407976.1:c.2232C>G NP_001394905.1:p.Cys744Trp missense NM_001407977.1:c.2232C>G NP_001394906.1:p.Cys744Trp missense NM_001407978.1:c.2232C>G NP_001394907.1:p.Cys744Trp missense NM_001407979.1:c.2229C>G NP_001394908.1:p.Cys743Trp missense NM_001407980.1:c.2229C>G NP_001394909.1:p.Cys743Trp missense NM_001407981.1:c.2229C>G NP_001394910.1:p.Cys743Trp missense NM_001407982.1:c.2229C>G NP_001394911.1:p.Cys743Trp missense NM_001407983.1:c.2229C>G NP_001394912.1:p.Cys743Trp missense NM_001407984.1:c.2229C>G NP_001394913.1:p.Cys743Trp missense NM_001407985.1:c.2229C>G NP_001394914.1:p.Cys743Trp missense NM_001407986.1:c.2229C>G NP_001394915.1:p.Cys743Trp missense NM_001407990.1:c.2229C>G NP_001394919.1:p.Cys743Trp missense NM_001407991.1:c.2229C>G NP_001394920.1:p.Cys743Trp missense NM_001407992.1:c.2229C>G NP_001394921.1:p.Cys743Trp missense NM_001407993.1:c.2229C>G NP_001394922.1:p.Cys743Trp missense NM_001408392.1:c.2226C>G NP_001395321.1:p.Cys742Trp missense NM_001408396.1:c.2226C>G NP_001395325.1:p.Cys742Trp missense NM_001408397.1:c.2226C>G NP_001395326.1:p.Cys742Trp missense NM_001408398.1:c.2226C>G NP_001395327.1:p.Cys742Trp missense NM_001408399.1:c.2226C>G NP_001395328.1:p.Cys742Trp missense NM_001408400.1:c.2226C>G NP_001395329.1:p.Cys742Trp missense NM_001408401.1:c.2226C>G NP_001395330.1:p.Cys742Trp missense NM_001408402.1:c.2226C>G NP_001395331.1:p.Cys742Trp missense NM_001408403.1:c.2226C>G NP_001395332.1:p.Cys742Trp missense NM_001408404.1:c.2226C>G NP_001395333.1:p.Cys742Trp missense NM_001408406.1:c.2223C>G NP_001395335.1:p.Cys741Trp missense NM_001408407.1:c.2223C>G NP_001395336.1:p.Cys741Trp missense NM_001408408.1:c.2223C>G NP_001395337.1:p.Cys741Trp missense NM_001408409.1:c.2220C>G NP_001395338.1:p.Cys740Trp missense NM_001408410.1:c.2157C>G NP_001395339.1:p.Cys719Trp missense NM_001408411.1:c.2154C>G NP_001395340.1:p.Cys718Trp missense NM_001408412.1:c.2151C>G NP_001395341.1:p.Cys717Trp missense NM_001408413.1:c.2151C>G NP_001395342.1:p.Cys717Trp missense NM_001408414.1:c.2151C>G NP_001395343.1:p.Cys717Trp missense NM_001408415.1:c.2151C>G NP_001395344.1:p.Cys717Trp missense NM_001408416.1:c.2151C>G NP_001395345.1:p.Cys717Trp missense NM_001408418.1:c.2115C>G NP_001395347.1:p.Cys705Trp missense NM_001408419.1:c.2115C>G NP_001395348.1:p.Cys705Trp missense NM_001408420.1:c.2115C>G NP_001395349.1:p.Cys705Trp missense NM_001408421.1:c.2112C>G NP_001395350.1:p.Cys704Trp missense NM_001408422.1:c.2112C>G NP_001395351.1:p.Cys704Trp missense NM_001408423.1:c.2112C>G NP_001395352.1:p.Cys704Trp missense NM_001408424.1:c.2112C>G NP_001395353.1:p.Cys704Trp missense NM_001408425.1:c.2109C>G NP_001395354.1:p.Cys703Trp missense NM_001408426.1:c.2109C>G NP_001395355.1:p.Cys703Trp missense NM_001408427.1:c.2109C>G NP_001395356.1:p.Cys703Trp missense NM_001408428.1:c.2109C>G NP_001395357.1:p.Cys703Trp missense NM_001408429.1:c.2109C>G NP_001395358.1:p.Cys703Trp missense NM_001408430.1:c.2109C>G NP_001395359.1:p.Cys703Trp missense NM_001408431.1:c.2109C>G NP_001395360.1:p.Cys703Trp missense NM_001408432.1:c.2106C>G NP_001395361.1:p.Cys702Trp missense NM_001408433.1:c.2106C>G NP_001395362.1:p.Cys702Trp missense NM_001408434.1:c.2106C>G NP_001395363.1:p.Cys702Trp missense NM_001408435.1:c.2106C>G NP_001395364.1:p.Cys702Trp missense NM_001408436.1:c.2106C>G NP_001395365.1:p.Cys702Trp missense NM_001408437.1:c.2106C>G NP_001395366.1:p.Cys702Trp missense NM_001408438.1:c.2106C>G NP_001395367.1:p.Cys702Trp missense NM_001408439.1:c.2106C>G NP_001395368.1:p.Cys702Trp missense NM_001408440.1:c.2106C>G NP_001395369.1:p.Cys702Trp missense NM_001408441.1:c.2106C>G NP_001395370.1:p.Cys702Trp missense NM_001408442.1:c.2106C>G NP_001395371.1:p.Cys702Trp missense NM_001408443.1:c.2106C>G NP_001395372.1:p.Cys702Trp missense NM_001408444.1:c.2106C>G NP_001395373.1:p.Cys702Trp missense NM_001408445.1:c.2103C>G NP_001395374.1:p.Cys701Trp missense NM_001408446.1:c.2103C>G NP_001395375.1:p.Cys701Trp missense NM_001408447.1:c.2103C>G NP_001395376.1:p.Cys701Trp missense NM_001408448.1:c.2103C>G NP_001395377.1:p.Cys701Trp missense NM_001408450.1:c.2103C>G NP_001395379.1:p.Cys701Trp missense NM_001408451.1:c.2097C>G NP_001395380.1:p.Cys699Trp missense NM_001408452.1:c.2091C>G NP_001395381.1:p.Cys697Trp missense NM_001408453.1:c.2091C>G NP_001395382.1:p.Cys697Trp missense NM_001408454.1:c.2091C>G NP_001395383.1:p.Cys697Trp missense NM_001408455.1:c.2091C>G NP_001395384.1:p.Cys697Trp missense NM_001408456.1:c.2091C>G NP_001395385.1:p.Cys697Trp missense NM_001408457.1:c.2091C>G NP_001395386.1:p.Cys697Trp missense NM_001408458.1:c.2088C>G NP_001395387.1:p.Cys696Trp missense NM_001408459.1:c.2088C>G NP_001395388.1:p.Cys696Trp missense NM_001408460.1:c.2088C>G NP_001395389.1:p.Cys696Trp missense NM_001408461.1:c.2088C>G NP_001395390.1:p.Cys696Trp missense NM_001408462.1:c.2088C>G NP_001395391.1:p.Cys696Trp missense NM_001408463.1:c.2088C>G NP_001395392.1:p.Cys696Trp missense NM_001408464.1:c.2088C>G NP_001395393.1:p.Cys696Trp missense NM_001408465.1:c.2088C>G NP_001395394.1:p.Cys696Trp missense NM_001408466.1:c.2088C>G NP_001395395.1:p.Cys696Trp missense NM_001408467.1:c.2088C>G NP_001395396.1:p.Cys696Trp missense NM_001408468.1:c.2085C>G NP_001395397.1:p.Cys695Trp missense NM_001408469.1:c.2085C>G NP_001395398.1:p.Cys695Trp missense NM_001408470.1:c.2085C>G NP_001395399.1:p.Cys695Trp missense NM_001408472.1:c.*55C>G NM_001408473.1:c.*55C>G NM_001408474.1:c.2031C>G NP_001395403.1:p.Cys677Trp missense NM_001408475.1:c.2028C>G NP_001395404.1:p.Cys676Trp missense NM_001408476.1:c.2028C>G NP_001395405.1:p.Cys676Trp missense NM_001408478.1:c.2022C>G NP_001395407.1:p.Cys674Trp missense NM_001408479.1:c.2022C>G NP_001395408.1:p.Cys674Trp missense NM_001408480.1:c.2022C>G NP_001395409.1:p.Cys674Trp missense NM_001408481.1:c.2019C>G NP_001395410.1:p.Cys673Trp missense NM_001408482.1:c.2019C>G NP_001395411.1:p.Cys673Trp missense NM_001408483.1:c.2019C>G NP_001395412.1:p.Cys673Trp missense NM_001408484.1:c.2019C>G NP_001395413.1:p.Cys673Trp missense NM_001408485.1:c.2019C>G NP_001395414.1:p.Cys673Trp missense NM_001408489.1:c.2019C>G NP_001395418.1:p.Cys673Trp missense NM_001408490.1:c.2019C>G NP_001395419.1:p.Cys673Trp missense NM_001408491.1:c.2019C>G NP_001395420.1:p.Cys673Trp missense NM_001408492.1:c.2016C>G NP_001395421.1:p.Cys672Trp missense NM_001408493.1:c.2016C>G NP_001395422.1:p.Cys672Trp missense NM_001408494.1:c.1992C>G NP_001395423.1:p.Cys664Trp missense NM_001408495.1:c.1986C>G NP_001395424.1:p.Cys662Trp missense NM_001408496.1:c.1968C>G NP_001395425.1:p.Cys656Trp missense NM_001408497.1:c.1968C>G NP_001395426.1:p.Cys656Trp missense NM_001408498.1:c.1968C>G NP_001395427.1:p.Cys656Trp missense NM_001408499.1:c.1968C>G NP_001395428.1:p.Cys656Trp missense NM_001408500.1:c.1968C>G NP_001395429.1:p.Cys656Trp missense NM_001408501.1:c.1968C>G NP_001395430.1:p.Cys656Trp missense NM_001408502.1:c.1965C>G NP_001395431.1:p.Cys655Trp missense NM_001408503.1:c.1965C>G NP_001395432.1:p.Cys655Trp missense NM_001408504.1:c.1965C>G NP_001395433.1:p.Cys655Trp missense NM_001408505.1:c.1962C>G NP_001395434.1:p.Cys654Trp missense NM_001408506.1:c.1905C>G NP_001395435.1:p.Cys635Trp missense NM_001408507.1:c.1902C>G NP_001395436.1:p.Cys634Trp missense NM_001408508.1:c.1893C>G NP_001395437.1:p.Cys631Trp missense NM_001408509.1:c.1890C>G NP_001395438.1:p.Cys630Trp missense NM_001408510.1:c.1851C>G NP_001395439.1:p.Cys617Trp missense NM_001408511.1:c.1848C>G NP_001395440.1:p.Cys616Trp missense NM_001408512.1:c.1728C>G NP_001395441.1:p.Cys576Trp missense NM_001408513.1:c.1701C>G NP_001395442.1:p.Cys567Trp missense NM_001408514.1:c.1305C>G NP_001395443.1:p.Cys435Trp missense NM_007297.4:c.5400C>G NP_009228.2:p.Cys1800Trp missense NM_007298.4:c.2229C>G NP_009229.2:p.Cys743Trp missense NM_007299.4:c.*55C>G 3 prime UTR NM_007300.4:c.5604C>G NP_009231.2:p.Cys1868Trp missense NM_007304.2:c.2229C>G NP_009235.2:p.Cys743Trp missense NR_027676.2:n.5718C>G non-coding transcript variant NC_000017.11:g.43045729G>C NC_000017.10:g.41197746G>C NG_005905.2:g.172255C>G LRG_292:g.172255C>G LRG_292t1:c.5541C>G LRG_292p1:p.Cys1847Trp - Protein change
- C1847W, C1800W, C1868W, C743W, C1550W, C1551W, C1693W, C1719W, C1734W, C1735W, C1736W, C1759W, C1779W, C1799W, C1805W, C1821W, C1827W, C1828W, C435W, C630W, C634W, C656W, C674W, C676W, C741W, C978W, C1718W, C1757W, C1777W, C1778W, C1803W, C1844W, C1867W, C655W, C672W, C697W, C718W, C719W, C1720W, C1758W, C1763W, C1780W, C1806W, C1842W, C1843W, C1845W, C1846W, C1869W, C617W, C635W, C654W, C664W, C677W, C696W, C699W, C701W, C704W, C705W, C717W, C740W, C979W, C1678W, C1775W, C1776W, C1798W, C1804W, C1819W, C1820W, C567W, C576W, C616W, C631W, C662W, C673W, C695W, C702W, C703W, C742W, C744W, C765W, C766W
- Other names
- -
- Canonical SPDI
- NC_000017.11:43045728:G:C
-
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.5541C>G, a MISSENSE variant, produced a function score of -0.13, 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
Exome Aggregation Consortium (ExAC) 0.00001
- 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. |
|---|---|---|---|---|
| not provided (1) |
no classification provided
|
- | RCV001077576.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 10, 2022 | RCV002554792.3 |
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
(Sep 10, 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: SCV003235686.2
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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) 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: 868637). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs397509295, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 1847 of the BRCA1 protein (p.Cys1847Trp). (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: SCV001243527.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.127904430808619
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Comment:
Germline Functional Evidence
| Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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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
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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: SCV001243527.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5541C>G, a MISSENSE variant, produced a function score of -0.13, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5541C>G, a MISSENSE variant, produced a function score of -0.13, 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:
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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) 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: 868637). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs397509295, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 1847 of the BRCA1 protein (p.Cys1847Trp).
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 rs397509295 ...
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 Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.