This missense variant replaces alanine with proline at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant protein is non-functional and results in decreased cell survival in a human haploid cell line-based assay (PMID: 30209399). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5365G>C (p.Ala1789Pro)
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)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
2
criteria provided, single submitter
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.5365G>C (p.Ala1789Pro)
Variation ID: 628780 Accession: VCV000628780.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43049162 (GRCh38) [ NCBI UCSC ] 17: 41201179 (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 May 20, 2019 Jun 19, 2021 Sep 8, 2020 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5365G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1789Pro missense NM_001407571.1:c.5152G>C NP_001394500.1:p.Ala1718Pro missense NM_001407581.1:c.5431G>C NP_001394510.1:p.Ala1811Pro missense NM_001407582.1:c.5431G>C NP_001394511.1:p.Ala1811Pro missense NM_001407583.1:c.5428G>C NP_001394512.1:p.Ala1810Pro missense NM_001407585.1:c.5428G>C NP_001394514.1:p.Ala1810Pro missense NM_001407587.1:c.5428G>C NP_001394516.1:p.Ala1810Pro missense NM_001407590.1:c.5425G>C NP_001394519.1:p.Ala1809Pro missense NM_001407591.1:c.5425G>C NP_001394520.1:p.Ala1809Pro missense NM_001407593.1:c.5365G>C NP_001394522.1:p.Ala1789Pro missense NM_001407594.1:c.5365G>C NP_001394523.1:p.Ala1789Pro missense NM_001407596.1:c.5365G>C NP_001394525.1:p.Ala1789Pro missense NM_001407597.1:c.5365G>C NP_001394526.1:p.Ala1789Pro missense NM_001407598.1:c.5365G>C NP_001394527.1:p.Ala1789Pro missense NM_001407602.1:c.5365G>C NP_001394531.1:p.Ala1789Pro missense NM_001407603.1:c.5365G>C NP_001394532.1:p.Ala1789Pro missense NM_001407605.1:c.5365G>C NP_001394534.1:p.Ala1789Pro missense NM_001407610.1:c.5362G>C NP_001394539.1:p.Ala1788Pro missense NM_001407611.1:c.5362G>C NP_001394540.1:p.Ala1788Pro missense NM_001407612.1:c.5362G>C NP_001394541.1:p.Ala1788Pro missense NM_001407613.1:c.5362G>C NP_001394542.1:p.Ala1788Pro missense NM_001407614.1:c.5362G>C NP_001394543.1:p.Ala1788Pro missense NM_001407615.1:c.5362G>C NP_001394544.1:p.Ala1788Pro missense NM_001407616.1:c.5362G>C NP_001394545.1:p.Ala1788Pro missense NM_001407617.1:c.5362G>C NP_001394546.1:p.Ala1788Pro missense NM_001407618.1:c.5362G>C NP_001394547.1:p.Ala1788Pro missense NM_001407619.1:c.5362G>C NP_001394548.1:p.Ala1788Pro missense NM_001407620.1:c.5362G>C NP_001394549.1:p.Ala1788Pro missense NM_001407621.1:c.5362G>C NP_001394550.1:p.Ala1788Pro missense NM_001407622.1:c.5362G>C NP_001394551.1:p.Ala1788Pro missense NM_001407623.1:c.5362G>C NP_001394552.1:p.Ala1788Pro missense NM_001407624.1:c.5362G>C NP_001394553.1:p.Ala1788Pro missense NM_001407625.1:c.5362G>C NP_001394554.1:p.Ala1788Pro missense NM_001407626.1:c.5362G>C NP_001394555.1:p.Ala1788Pro missense NM_001407627.1:c.5359G>C NP_001394556.1:p.Ala1787Pro missense NM_001407628.1:c.5359G>C NP_001394557.1:p.Ala1787Pro missense NM_001407629.1:c.5359G>C NP_001394558.1:p.Ala1787Pro missense NM_001407630.1:c.5359G>C NP_001394559.1:p.Ala1787Pro missense NM_001407631.1:c.5359G>C NP_001394560.1:p.Ala1787Pro missense NM_001407632.1:c.5359G>C NP_001394561.1:p.Ala1787Pro missense NM_001407633.1:c.5359G>C NP_001394562.1:p.Ala1787Pro missense NM_001407634.1:c.5359G>C NP_001394563.1:p.Ala1787Pro missense NM_001407635.1:c.5359G>C NP_001394564.1:p.Ala1787Pro missense NM_001407636.1:c.5359G>C NP_001394565.1:p.Ala1787Pro missense NM_001407637.1:c.5359G>C NP_001394566.1:p.Ala1787Pro missense NM_001407638.1:c.5359G>C NP_001394567.1:p.Ala1787Pro missense NM_001407639.1:c.5359G>C NP_001394568.1:p.Ala1787Pro missense NM_001407640.1:c.5359G>C NP_001394569.1:p.Ala1787Pro missense NM_001407641.1:c.5359G>C NP_001394570.1:p.Ala1787Pro missense NM_001407642.1:c.5359G>C NP_001394571.1:p.Ala1787Pro missense NM_001407644.1:c.5356G>C NP_001394573.1:p.Ala1786Pro missense NM_001407645.1:c.5356G>C NP_001394574.1:p.Ala1786Pro missense NM_001407646.1:c.5353G>C NP_001394575.1:p.Ala1785Pro missense NM_001407647.1:c.5350G>C NP_001394576.1:p.Ala1784Pro missense NM_001407648.1:c.5308G>C NP_001394577.1:p.Ala1770Pro missense NM_001407649.1:c.5305G>C NP_001394578.1:p.Ala1769Pro missense NM_001407652.1:c.5287G>C NP_001394581.1:p.Ala1763Pro missense NM_001407653.1:c.5287G>C NP_001394582.1:p.Ala1763Pro missense NM_001407654.1:c.5287G>C NP_001394583.1:p.Ala1763Pro missense NM_001407655.1:c.5287G>C NP_001394584.1:p.Ala1763Pro missense NM_001407656.1:c.5284G>C NP_001394585.1:p.Ala1762Pro missense NM_001407657.1:c.5284G>C NP_001394586.1:p.Ala1762Pro missense NM_001407658.1:c.5284G>C NP_001394587.1:p.Ala1762Pro missense NM_001407659.1:c.5281G>C NP_001394588.1:p.Ala1761Pro missense NM_001407660.1:c.5281G>C NP_001394589.1:p.Ala1761Pro missense NM_001407661.1:c.5281G>C NP_001394590.1:p.Ala1761Pro missense NM_001407662.1:c.5281G>C NP_001394591.1:p.Ala1761Pro missense NM_001407663.1:c.5281G>C NP_001394592.1:p.Ala1761Pro missense NM_001407664.1:c.5242G>C NP_001394593.1:p.Ala1748Pro missense NM_001407665.1:c.5242G>C NP_001394594.1:p.Ala1748Pro missense NM_001407666.1:c.5242G>C NP_001394595.1:p.Ala1748Pro missense NM_001407667.1:c.5242G>C NP_001394596.1:p.Ala1748Pro missense NM_001407668.1:c.5242G>C NP_001394597.1:p.Ala1748Pro missense NM_001407669.1:c.5242G>C NP_001394598.1:p.Ala1748Pro missense NM_001407670.1:c.5239G>C NP_001394599.1:p.Ala1747Pro missense NM_001407671.1:c.5239G>C NP_001394600.1:p.Ala1747Pro missense NM_001407672.1:c.5239G>C NP_001394601.1:p.Ala1747Pro missense NM_001407673.1:c.5239G>C NP_001394602.1:p.Ala1747Pro missense NM_001407674.1:c.5239G>C NP_001394603.1:p.Ala1747Pro missense NM_001407675.1:c.5239G>C NP_001394604.1:p.Ala1747Pro missense NM_001407676.1:c.5239G>C NP_001394605.1:p.Ala1747Pro missense NM_001407677.1:c.5239G>C NP_001394606.1:p.Ala1747Pro missense NM_001407678.1:c.5239G>C NP_001394607.1:p.Ala1747Pro missense NM_001407679.1:c.5239G>C NP_001394608.1:p.Ala1747Pro missense NM_001407680.1:c.5239G>C NP_001394609.1:p.Ala1747Pro missense NM_001407681.1:c.5236G>C NP_001394610.1:p.Ala1746Pro missense NM_001407682.1:c.5236G>C NP_001394611.1:p.Ala1746Pro missense NM_001407683.1:c.5236G>C NP_001394612.1:p.Ala1746Pro missense NM_001407685.1:c.5236G>C NP_001394614.1:p.Ala1746Pro missense NM_001407686.1:c.5236G>C NP_001394615.1:p.Ala1746Pro missense NM_001407687.1:c.5236G>C NP_001394616.1:p.Ala1746Pro missense NM_001407688.1:c.5236G>C NP_001394617.1:p.Ala1746Pro missense NM_001407689.1:c.5236G>C NP_001394618.1:p.Ala1746Pro missense NM_001407690.1:c.5233G>C NP_001394619.1:p.Ala1745Pro missense NM_001407691.1:c.5233G>C NP_001394620.1:p.Ala1745Pro missense NM_001407692.1:c.5224G>C NP_001394621.1:p.Ala1742Pro missense NM_001407694.1:c.5224G>C NP_001394623.1:p.Ala1742Pro missense NM_001407695.1:c.5224G>C NP_001394624.1:p.Ala1742Pro missense NM_001407696.1:c.5224G>C NP_001394625.1:p.Ala1742Pro missense NM_001407697.1:c.5224G>C NP_001394626.1:p.Ala1742Pro missense NM_001407698.1:c.5224G>C NP_001394627.1:p.Ala1742Pro missense NM_001407724.1:c.5224G>C NP_001394653.1:p.Ala1742Pro missense NM_001407725.1:c.5224G>C NP_001394654.1:p.Ala1742Pro missense NM_001407726.1:c.5224G>C NP_001394655.1:p.Ala1742Pro missense NM_001407727.1:c.5224G>C NP_001394656.1:p.Ala1742Pro missense NM_001407728.1:c.5224G>C NP_001394657.1:p.Ala1742Pro missense NM_001407729.1:c.5224G>C NP_001394658.1:p.Ala1742Pro missense NM_001407730.1:c.5224G>C NP_001394659.1:p.Ala1742Pro missense NM_001407731.1:c.5224G>C NP_001394660.1:p.Ala1742Pro missense NM_001407732.1:c.5221G>C NP_001394661.1:p.Ala1741Pro missense NM_001407733.1:c.5221G>C NP_001394662.1:p.Ala1741Pro missense NM_001407734.1:c.5221G>C NP_001394663.1:p.Ala1741Pro missense NM_001407735.1:c.5221G>C NP_001394664.1:p.Ala1741Pro missense NM_001407736.1:c.5221G>C NP_001394665.1:p.Ala1741Pro missense NM_001407737.1:c.5221G>C NP_001394666.1:p.Ala1741Pro missense NM_001407738.1:c.5221G>C NP_001394667.1:p.Ala1741Pro missense NM_001407739.1:c.5221G>C NP_001394668.1:p.Ala1741Pro missense NM_001407740.1:c.5221G>C NP_001394669.1:p.Ala1741Pro missense NM_001407741.1:c.5221G>C NP_001394670.1:p.Ala1741Pro missense NM_001407742.1:c.5221G>C NP_001394671.1:p.Ala1741Pro missense NM_001407743.1:c.5221G>C NP_001394672.1:p.Ala1741Pro missense NM_001407744.1:c.5221G>C NP_001394673.1:p.Ala1741Pro missense NM_001407745.1:c.5221G>C NP_001394674.1:p.Ala1741Pro missense NM_001407746.1:c.5221G>C NP_001394675.1:p.Ala1741Pro missense NM_001407747.1:c.5221G>C NP_001394676.1:p.Ala1741Pro missense NM_001407748.1:c.5221G>C NP_001394677.1:p.Ala1741Pro missense NM_001407749.1:c.5221G>C NP_001394678.1:p.Ala1741Pro missense NM_001407750.1:c.5221G>C NP_001394679.1:p.Ala1741Pro missense NM_001407751.1:c.5221G>C NP_001394680.1:p.Ala1741Pro missense NM_001407752.1:c.5221G>C NP_001394681.1:p.Ala1741Pro missense NM_001407838.1:c.5218G>C NP_001394767.1:p.Ala1740Pro missense NM_001407839.1:c.5218G>C NP_001394768.1:p.Ala1740Pro missense NM_001407841.1:c.5218G>C NP_001394770.1:p.Ala1740Pro missense NM_001407842.1:c.5218G>C NP_001394771.1:p.Ala1740Pro missense NM_001407843.1:c.5218G>C NP_001394772.1:p.Ala1740Pro missense NM_001407844.1:c.5218G>C NP_001394773.1:p.Ala1740Pro missense NM_001407845.1:c.5218G>C NP_001394774.1:p.Ala1740Pro missense NM_001407846.1:c.5218G>C NP_001394775.1:p.Ala1740Pro missense NM_001407847.1:c.5218G>C NP_001394776.1:p.Ala1740Pro missense NM_001407848.1:c.5218G>C NP_001394777.1:p.Ala1740Pro missense NM_001407849.1:c.5218G>C NP_001394778.1:p.Ala1740Pro missense NM_001407850.1:c.5218G>C NP_001394779.1:p.Ala1740Pro missense NM_001407851.1:c.5218G>C NP_001394780.1:p.Ala1740Pro missense NM_001407852.1:c.5218G>C NP_001394781.1:p.Ala1740Pro missense NM_001407853.1:c.5218G>C NP_001394782.1:p.Ala1740Pro missense NM_001407862.1:c.5164G>C NP_001394791.1:p.Ala1722Pro missense NM_001407863.1:c.5161G>C NP_001394792.1:p.Ala1721Pro missense NM_001407874.1:c.5158G>C NP_001394803.1:p.Ala1720Pro missense NM_001407875.1:c.5158G>C NP_001394804.1:p.Ala1720Pro missense NM_001407879.1:c.5155G>C NP_001394808.1:p.Ala1719Pro missense NM_001407881.1:c.5155G>C NP_001394810.1:p.Ala1719Pro missense NM_001407882.1:c.5155G>C NP_001394811.1:p.Ala1719Pro missense NM_001407884.1:c.5155G>C NP_001394813.1:p.Ala1719Pro missense NM_001407885.1:c.5155G>C NP_001394814.1:p.Ala1719Pro missense NM_001407886.1:c.5155G>C NP_001394815.1:p.Ala1719Pro missense NM_001407887.1:c.5155G>C NP_001394816.1:p.Ala1719Pro missense NM_001407889.1:c.5155G>C NP_001394818.1:p.Ala1719Pro missense NM_001407894.1:c.5152G>C NP_001394823.1:p.Ala1718Pro missense NM_001407895.1:c.5152G>C NP_001394824.1:p.Ala1718Pro missense NM_001407896.1:c.5152G>C NP_001394825.1:p.Ala1718Pro missense NM_001407897.1:c.5152G>C NP_001394826.1:p.Ala1718Pro missense NM_001407898.1:c.5152G>C NP_001394827.1:p.Ala1718Pro missense NM_001407899.1:c.5152G>C NP_001394828.1:p.Ala1718Pro missense NM_001407900.1:c.5152G>C NP_001394829.1:p.Ala1718Pro missense NM_001407902.1:c.5152G>C NP_001394831.1:p.Ala1718Pro missense NM_001407904.1:c.5152G>C NP_001394833.1:p.Ala1718Pro missense NM_001407906.1:c.5152G>C NP_001394835.1:p.Ala1718Pro missense NM_001407907.1:c.5152G>C NP_001394836.1:p.Ala1718Pro missense NM_001407908.1:c.5152G>C NP_001394837.1:p.Ala1718Pro missense NM_001407909.1:c.5152G>C NP_001394838.1:p.Ala1718Pro missense NM_001407910.1:c.5152G>C NP_001394839.1:p.Ala1718Pro missense NM_001407915.1:c.5149G>C NP_001394844.1:p.Ala1717Pro missense NM_001407916.1:c.5149G>C NP_001394845.1:p.Ala1717Pro missense NM_001407917.1:c.5149G>C NP_001394846.1:p.Ala1717Pro missense NM_001407918.1:c.5149G>C NP_001394847.1:p.Ala1717Pro missense NM_001407920.1:c.5101G>C NP_001394849.1:p.Ala1701Pro missense NM_001407921.1:c.5101G>C NP_001394850.1:p.Ala1701Pro missense NM_001407922.1:c.5101G>C NP_001394851.1:p.Ala1701Pro missense NM_001407923.1:c.5101G>C NP_001394852.1:p.Ala1701Pro missense NM_001407924.1:c.5101G>C NP_001394853.1:p.Ala1701Pro missense NM_001407925.1:c.5101G>C NP_001394854.1:p.Ala1701Pro missense NM_001407926.1:c.5101G>C NP_001394855.1:p.Ala1701Pro missense NM_001407927.1:c.5098G>C NP_001394856.1:p.Ala1700Pro missense NM_001407928.1:c.5098G>C NP_001394857.1:p.Ala1700Pro missense NM_001407929.1:c.5098G>C NP_001394858.1:p.Ala1700Pro missense NM_001407930.1:c.5098G>C NP_001394859.1:p.Ala1700Pro missense NM_001407931.1:c.5098G>C NP_001394860.1:p.Ala1700Pro missense NM_001407932.1:c.5098G>C NP_001394861.1:p.Ala1700Pro missense NM_001407933.1:c.5098G>C NP_001394862.1:p.Ala1700Pro missense NM_001407934.1:c.5095G>C NP_001394863.1:p.Ala1699Pro missense NM_001407935.1:c.5095G>C NP_001394864.1:p.Ala1699Pro missense NM_001407936.1:c.5095G>C NP_001394865.1:p.Ala1699Pro missense NM_001407946.1:c.5032G>C NP_001394875.1:p.Ala1678Pro missense NM_001407947.1:c.5032G>C NP_001394876.1:p.Ala1678Pro missense NM_001407948.1:c.5032G>C NP_001394877.1:p.Ala1678Pro missense NM_001407949.1:c.5032G>C NP_001394878.1:p.Ala1678Pro missense NM_001407950.1:c.5029G>C NP_001394879.1:p.Ala1677Pro missense NM_001407951.1:c.5029G>C NP_001394880.1:p.Ala1677Pro missense NM_001407952.1:c.5029G>C NP_001394881.1:p.Ala1677Pro missense NM_001407953.1:c.5029G>C NP_001394882.1:p.Ala1677Pro missense NM_001407954.1:c.5029G>C NP_001394883.1:p.Ala1677Pro missense NM_001407955.1:c.5029G>C NP_001394884.1:p.Ala1677Pro missense NM_001407956.1:c.5026G>C NP_001394885.1:p.Ala1676Pro missense NM_001407957.1:c.5026G>C NP_001394886.1:p.Ala1676Pro missense NM_001407958.1:c.5026G>C NP_001394887.1:p.Ala1676Pro missense NM_001407959.1:c.4984G>C NP_001394888.1:p.Ala1662Pro missense NM_001407960.1:c.4981G>C NP_001394889.1:p.Ala1661Pro missense NM_001407962.1:c.4981G>C NP_001394891.1:p.Ala1661Pro missense NM_001407963.1:c.4978G>C NP_001394892.1:p.Ala1660Pro missense NM_001407964.1:c.4903G>C NP_001394893.1:p.Ala1635Pro missense NM_001407965.1:c.4858G>C NP_001394894.1:p.Ala1620Pro missense NM_001407966.1:c.4477G>C NP_001394895.1:p.Ala1493Pro missense NM_001407967.1:c.4474G>C NP_001394896.1:p.Ala1492Pro missense NM_001407968.1:c.2761G>C NP_001394897.1:p.Ala921Pro missense NM_001407969.1:c.2758G>C NP_001394898.1:p.Ala920Pro missense NM_001407970.1:c.2122G>C NP_001394899.1:p.Ala708Pro missense NM_001407971.1:c.2122G>C NP_001394900.1:p.Ala708Pro missense NM_001407972.1:c.2119G>C NP_001394901.1:p.Ala707Pro missense NM_001407973.1:c.2056G>C NP_001394902.1:p.Ala686Pro missense NM_001407974.1:c.2056G>C NP_001394903.1:p.Ala686Pro missense NM_001407975.1:c.2056G>C NP_001394904.1:p.Ala686Pro missense NM_001407976.1:c.2056G>C NP_001394905.1:p.Ala686Pro missense NM_001407977.1:c.2056G>C NP_001394906.1:p.Ala686Pro missense NM_001407978.1:c.2056G>C NP_001394907.1:p.Ala686Pro missense NM_001407979.1:c.2053G>C NP_001394908.1:p.Ala685Pro missense NM_001407980.1:c.2053G>C NP_001394909.1:p.Ala685Pro missense NM_001407981.1:c.2053G>C NP_001394910.1:p.Ala685Pro missense NM_001407982.1:c.2053G>C NP_001394911.1:p.Ala685Pro missense NM_001407983.1:c.2053G>C NP_001394912.1:p.Ala685Pro missense NM_001407984.1:c.2053G>C NP_001394913.1:p.Ala685Pro missense NM_001407985.1:c.2053G>C NP_001394914.1:p.Ala685Pro missense NM_001407986.1:c.2053G>C NP_001394915.1:p.Ala685Pro missense NM_001407990.1:c.2053G>C NP_001394919.1:p.Ala685Pro missense NM_001407991.1:c.2053G>C NP_001394920.1:p.Ala685Pro missense NM_001407992.1:c.2053G>C NP_001394921.1:p.Ala685Pro missense NM_001407993.1:c.2053G>C NP_001394922.1:p.Ala685Pro missense NM_001408392.1:c.2050G>C NP_001395321.1:p.Ala684Pro missense NM_001408396.1:c.2050G>C NP_001395325.1:p.Ala684Pro missense NM_001408397.1:c.2050G>C NP_001395326.1:p.Ala684Pro missense NM_001408398.1:c.2050G>C NP_001395327.1:p.Ala684Pro missense NM_001408399.1:c.2050G>C NP_001395328.1:p.Ala684Pro missense NM_001408400.1:c.2050G>C NP_001395329.1:p.Ala684Pro missense NM_001408401.1:c.2050G>C NP_001395330.1:p.Ala684Pro missense NM_001408402.1:c.2050G>C NP_001395331.1:p.Ala684Pro missense NM_001408403.1:c.2050G>C NP_001395332.1:p.Ala684Pro missense NM_001408404.1:c.2050G>C NP_001395333.1:p.Ala684Pro missense NM_001408406.1:c.2047G>C NP_001395335.1:p.Ala683Pro missense NM_001408407.1:c.2047G>C NP_001395336.1:p.Ala683Pro missense NM_001408408.1:c.2047G>C NP_001395337.1:p.Ala683Pro missense NM_001408409.1:c.2044G>C NP_001395338.1:p.Ala682Pro missense NM_001408410.1:c.1981G>C NP_001395339.1:p.Ala661Pro missense NM_001408411.1:c.1978G>C NP_001395340.1:p.Ala660Pro missense NM_001408412.1:c.1975G>C NP_001395341.1:p.Ala659Pro missense NM_001408413.1:c.1975G>C NP_001395342.1:p.Ala659Pro missense NM_001408414.1:c.1975G>C NP_001395343.1:p.Ala659Pro missense NM_001408415.1:c.1975G>C NP_001395344.1:p.Ala659Pro missense NM_001408416.1:c.1975G>C NP_001395345.1:p.Ala659Pro missense NM_001408418.1:c.1939G>C NP_001395347.1:p.Ala647Pro missense NM_001408419.1:c.1939G>C NP_001395348.1:p.Ala647Pro missense NM_001408420.1:c.1939G>C NP_001395349.1:p.Ala647Pro missense NM_001408421.1:c.1936G>C NP_001395350.1:p.Ala646Pro missense NM_001408422.1:c.1936G>C NP_001395351.1:p.Ala646Pro missense NM_001408423.1:c.1936G>C NP_001395352.1:p.Ala646Pro missense NM_001408424.1:c.1936G>C NP_001395353.1:p.Ala646Pro missense NM_001408425.1:c.1933G>C NP_001395354.1:p.Ala645Pro missense NM_001408426.1:c.1933G>C NP_001395355.1:p.Ala645Pro missense NM_001408427.1:c.1933G>C NP_001395356.1:p.Ala645Pro missense NM_001408428.1:c.1933G>C NP_001395357.1:p.Ala645Pro missense NM_001408429.1:c.1933G>C NP_001395358.1:p.Ala645Pro missense NM_001408430.1:c.1933G>C NP_001395359.1:p.Ala645Pro missense NM_001408431.1:c.1933G>C NP_001395360.1:p.Ala645Pro missense NM_001408432.1:c.1930G>C NP_001395361.1:p.Ala644Pro missense NM_001408433.1:c.1930G>C NP_001395362.1:p.Ala644Pro missense NM_001408434.1:c.1930G>C NP_001395363.1:p.Ala644Pro missense NM_001408435.1:c.1930G>C NP_001395364.1:p.Ala644Pro missense NM_001408436.1:c.1930G>C NP_001395365.1:p.Ala644Pro missense NM_001408437.1:c.1930G>C NP_001395366.1:p.Ala644Pro missense NM_001408438.1:c.1930G>C NP_001395367.1:p.Ala644Pro missense NM_001408439.1:c.1930G>C NP_001395368.1:p.Ala644Pro missense NM_001408440.1:c.1930G>C NP_001395369.1:p.Ala644Pro missense NM_001408441.1:c.1930G>C NP_001395370.1:p.Ala644Pro missense NM_001408442.1:c.1930G>C NP_001395371.1:p.Ala644Pro missense NM_001408443.1:c.1930G>C NP_001395372.1:p.Ala644Pro missense NM_001408444.1:c.1930G>C NP_001395373.1:p.Ala644Pro missense NM_001408445.1:c.1927G>C NP_001395374.1:p.Ala643Pro missense NM_001408446.1:c.1927G>C NP_001395375.1:p.Ala643Pro missense NM_001408447.1:c.1927G>C NP_001395376.1:p.Ala643Pro missense NM_001408448.1:c.1927G>C NP_001395377.1:p.Ala643Pro missense NM_001408450.1:c.1927G>C NP_001395379.1:p.Ala643Pro missense NM_001408451.1:c.1921G>C NP_001395380.1:p.Ala641Pro missense NM_001408452.1:c.1915G>C NP_001395381.1:p.Ala639Pro missense NM_001408453.1:c.1915G>C NP_001395382.1:p.Ala639Pro missense NM_001408454.1:c.1915G>C NP_001395383.1:p.Ala639Pro missense NM_001408455.1:c.1915G>C NP_001395384.1:p.Ala639Pro missense NM_001408456.1:c.1915G>C NP_001395385.1:p.Ala639Pro missense NM_001408457.1:c.1915G>C NP_001395386.1:p.Ala639Pro missense NM_001408458.1:c.1912G>C NP_001395387.1:p.Ala638Pro missense NM_001408459.1:c.1912G>C NP_001395388.1:p.Ala638Pro missense NM_001408460.1:c.1912G>C NP_001395389.1:p.Ala638Pro missense NM_001408461.1:c.1912G>C NP_001395390.1:p.Ala638Pro missense NM_001408462.1:c.1912G>C NP_001395391.1:p.Ala638Pro missense NM_001408463.1:c.1912G>C NP_001395392.1:p.Ala638Pro missense NM_001408464.1:c.1912G>C NP_001395393.1:p.Ala638Pro missense NM_001408465.1:c.1912G>C NP_001395394.1:p.Ala638Pro missense NM_001408466.1:c.1912G>C NP_001395395.1:p.Ala638Pro missense NM_001408467.1:c.1912G>C NP_001395396.1:p.Ala638Pro missense NM_001408468.1:c.1909G>C NP_001395397.1:p.Ala637Pro missense NM_001408469.1:c.1909G>C NP_001395398.1:p.Ala637Pro missense NM_001408470.1:c.1909G>C NP_001395399.1:p.Ala637Pro missense NM_001408474.1:c.1855G>C NP_001395403.1:p.Ala619Pro missense NM_001408475.1:c.1852G>C NP_001395404.1:p.Ala618Pro missense NM_001408476.1:c.1852G>C NP_001395405.1:p.Ala618Pro missense NM_001408478.1:c.1846G>C NP_001395407.1:p.Ala616Pro missense NM_001408479.1:c.1846G>C NP_001395408.1:p.Ala616Pro missense NM_001408480.1:c.1846G>C NP_001395409.1:p.Ala616Pro missense NM_001408481.1:c.1843G>C NP_001395410.1:p.Ala615Pro missense NM_001408482.1:c.1843G>C NP_001395411.1:p.Ala615Pro missense NM_001408483.1:c.1843G>C NP_001395412.1:p.Ala615Pro missense NM_001408484.1:c.1843G>C NP_001395413.1:p.Ala615Pro missense NM_001408485.1:c.1843G>C NP_001395414.1:p.Ala615Pro missense NM_001408489.1:c.1843G>C NP_001395418.1:p.Ala615Pro missense NM_001408490.1:c.1843G>C NP_001395419.1:p.Ala615Pro missense NM_001408491.1:c.1843G>C NP_001395420.1:p.Ala615Pro missense NM_001408492.1:c.1840G>C NP_001395421.1:p.Ala614Pro missense NM_001408493.1:c.1840G>C NP_001395422.1:p.Ala614Pro missense NM_001408494.1:c.1816G>C NP_001395423.1:p.Ala606Pro missense NM_001408495.1:c.1810G>C NP_001395424.1:p.Ala604Pro missense NM_001408496.1:c.1792G>C NP_001395425.1:p.Ala598Pro missense NM_001408497.1:c.1792G>C NP_001395426.1:p.Ala598Pro missense NM_001408498.1:c.1792G>C NP_001395427.1:p.Ala598Pro missense NM_001408499.1:c.1792G>C NP_001395428.1:p.Ala598Pro missense NM_001408500.1:c.1792G>C NP_001395429.1:p.Ala598Pro missense NM_001408501.1:c.1792G>C NP_001395430.1:p.Ala598Pro missense NM_001408502.1:c.1789G>C NP_001395431.1:p.Ala597Pro missense NM_001408503.1:c.1789G>C NP_001395432.1:p.Ala597Pro missense NM_001408504.1:c.1789G>C NP_001395433.1:p.Ala597Pro missense NM_001408505.1:c.1786G>C NP_001395434.1:p.Ala596Pro missense NM_001408506.1:c.1729G>C NP_001395435.1:p.Ala577Pro missense NM_001408507.1:c.1726G>C NP_001395436.1:p.Ala576Pro missense NM_001408508.1:c.1717G>C NP_001395437.1:p.Ala573Pro missense NM_001408509.1:c.1714G>C NP_001395438.1:p.Ala572Pro missense NM_001408510.1:c.1675G>C NP_001395439.1:p.Ala559Pro missense NM_001408511.1:c.1672G>C NP_001395440.1:p.Ala558Pro missense NM_001408512.1:c.1552G>C NP_001395441.1:p.Ala518Pro missense NM_001408513.1:c.1525G>C NP_001395442.1:p.Ala509Pro missense NM_001408514.1:c.1129G>C NP_001395443.1:p.Ala377Pro missense NM_007297.4:c.5224G>C NP_009228.2:p.Ala1742Pro missense NM_007298.4:c.2053G>C NP_009229.2:p.Ala685Pro missense NM_007299.4:c.2021-1459G>C intron variant NM_007300.4:c.5428G>C NP_009231.2:p.Ala1810Pro missense NM_007304.2:c.2053G>C NP_009235.2:p.Ala685Pro missense NR_027676.2:n.5542G>C non-coding transcript variant NC_000017.11:g.43049162C>G NC_000017.10:g.41201179C>G NG_005905.2:g.168822G>C LRG_292:g.168822G>C LRG_292t1:c.5365G>C LRG_292p1:p.Ala1789Pro - Protein change
- A1789P, A1810P, A1742P, A685P, A1662P, A1677P, A1700P, A1701P, A1717P, A1718P, A1719P, A1748P, A1761P, A1762P, A1770P, A1809P, A377P, A509P, A559P, A606P, A614P, A618P, A619P, A637P, A644P, A659P, A661P, A682P, A684P, A686P, A1661P, A1492P, A1720P, A1746P, A1763P, A1788P, A597P, A615P, A639P, A641P, A643P, A645P, A660P, A921P, A1745P, A1747P, A1784P, A1785P, A1811P, A518P, A558P, A572P, A576P, A598P, A604P, A616P, A638P, A646P, A647P, A683P, A707P, A708P, A920P, A1493P, A1620P, A1676P, A1678P, A1699P, A1722P, A1740P, A1635P, A1660P, A1721P, A1741P, A1769P, A1786P, A1787P, A573P, A577P, A596P
- Other names
- -
- Canonical SPDI
- NC_000017.11:43049161:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>C, a MISSENSE variant, produced a function score of -1.67, corresponding to a functional classification of LOSS_OF_FUNCTION. 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.
- -
- 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
|
Sep 8, 2020 | RCV000773443.4 | |
| not provided (1) |
no classification provided
|
- | RCV001077271.3 |
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 08, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000907137.2
First in ClinVar: May 20, 2019 Last updated: Jun 19, 2021 |
Comment:
This missense variant replaces alanine with proline at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces alanine with proline at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant protein is non-functional and results in decreased cell survival in a human haploid cell line-based assay (PMID: 30209399). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (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: SCV001243175.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-1.67132779442868
|
Comment:
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
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
functionally_abnormal
|
Method citation(s):
|
|
Brotman Baty Institute, University of Washington
Accession: SCV001243175.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>C, a MISSENSE variant, produced a function score of -1.67, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>C, a MISSENSE variant, produced a function score of -1.67, corresponding to a functional classification of LOSS_OF_FUNCTION. 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)
|
Comment:
This missense variant replaces alanine with proline at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant protein is non-functional and results in decreased cell survival in a human haploid cell line-based assay (PMID: 30209399). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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 rs80357078 ...
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.