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 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. ClinVar contains an entry for this variant (Variation ID: 868199). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1742 of the BRCA1 protein (p.Asn1742His).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5224A>C (p.Asn1742His)
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.5224A>C (p.Asn1742His)
Variation ID: 868199 Accession: VCV000868199.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43057105 (GRCh38) [ NCBI UCSC ] 17: 41209122 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 May 9, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5224A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asn1742His missense NM_001407571.1:c.5011A>C NP_001394500.1:p.Asn1671His missense NM_001407581.1:c.5290A>C NP_001394510.1:p.Asn1764His missense NM_001407582.1:c.5290A>C NP_001394511.1:p.Asn1764His missense NM_001407583.1:c.5287A>C NP_001394512.1:p.Asn1763His missense NM_001407585.1:c.5287A>C NP_001394514.1:p.Asn1763His missense NM_001407587.1:c.5287A>C NP_001394516.1:p.Asn1763His missense NM_001407590.1:c.5284A>C NP_001394519.1:p.Asn1762His missense NM_001407591.1:c.5284A>C NP_001394520.1:p.Asn1762His missense NM_001407593.1:c.5224A>C NP_001394522.1:p.Asn1742His missense NM_001407594.1:c.5224A>C NP_001394523.1:p.Asn1742His missense NM_001407596.1:c.5224A>C NP_001394525.1:p.Asn1742His missense NM_001407597.1:c.5224A>C NP_001394526.1:p.Asn1742His missense NM_001407598.1:c.5224A>C NP_001394527.1:p.Asn1742His missense NM_001407602.1:c.5224A>C NP_001394531.1:p.Asn1742His missense NM_001407603.1:c.5224A>C NP_001394532.1:p.Asn1742His missense NM_001407605.1:c.5224A>C NP_001394534.1:p.Asn1742His missense NM_001407610.1:c.5221A>C NP_001394539.1:p.Asn1741His missense NM_001407611.1:c.5221A>C NP_001394540.1:p.Asn1741His missense NM_001407612.1:c.5221A>C NP_001394541.1:p.Asn1741His missense NM_001407613.1:c.5221A>C NP_001394542.1:p.Asn1741His missense NM_001407614.1:c.5221A>C NP_001394543.1:p.Asn1741His missense NM_001407615.1:c.5221A>C NP_001394544.1:p.Asn1741His missense NM_001407616.1:c.5221A>C NP_001394545.1:p.Asn1741His missense NM_001407617.1:c.5221A>C NP_001394546.1:p.Asn1741His missense NM_001407618.1:c.5221A>C NP_001394547.1:p.Asn1741His missense NM_001407619.1:c.5221A>C NP_001394548.1:p.Asn1741His missense NM_001407620.1:c.5221A>C NP_001394549.1:p.Asn1741His missense NM_001407621.1:c.5221A>C NP_001394550.1:p.Asn1741His missense NM_001407622.1:c.5221A>C NP_001394551.1:p.Asn1741His missense NM_001407623.1:c.5221A>C NP_001394552.1:p.Asn1741His missense NM_001407624.1:c.5221A>C NP_001394553.1:p.Asn1741His missense NM_001407625.1:c.5221A>C NP_001394554.1:p.Asn1741His missense NM_001407626.1:c.5221A>C NP_001394555.1:p.Asn1741His missense NM_001407627.1:c.5218A>C NP_001394556.1:p.Asn1740His missense NM_001407628.1:c.5218A>C NP_001394557.1:p.Asn1740His missense NM_001407629.1:c.5218A>C NP_001394558.1:p.Asn1740His missense NM_001407630.1:c.5218A>C NP_001394559.1:p.Asn1740His missense NM_001407631.1:c.5218A>C NP_001394560.1:p.Asn1740His missense NM_001407632.1:c.5218A>C NP_001394561.1:p.Asn1740His missense NM_001407633.1:c.5218A>C NP_001394562.1:p.Asn1740His missense NM_001407634.1:c.5218A>C NP_001394563.1:p.Asn1740His missense NM_001407635.1:c.5218A>C NP_001394564.1:p.Asn1740His missense NM_001407636.1:c.5218A>C NP_001394565.1:p.Asn1740His missense NM_001407637.1:c.5218A>C NP_001394566.1:p.Asn1740His missense NM_001407638.1:c.5218A>C NP_001394567.1:p.Asn1740His missense NM_001407639.1:c.5218A>C NP_001394568.1:p.Asn1740His missense NM_001407640.1:c.5218A>C NP_001394569.1:p.Asn1740His missense NM_001407641.1:c.5218A>C NP_001394570.1:p.Asn1740His missense NM_001407642.1:c.5218A>C NP_001394571.1:p.Asn1740His missense NM_001407644.1:c.5215A>C NP_001394573.1:p.Asn1739His missense NM_001407645.1:c.5215A>C NP_001394574.1:p.Asn1739His missense NM_001407646.1:c.5212A>C NP_001394575.1:p.Asn1738His missense NM_001407647.1:c.5209A>C NP_001394576.1:p.Asn1737His missense NM_001407648.1:c.5167A>C NP_001394577.1:p.Asn1723His missense NM_001407649.1:c.5164A>C NP_001394578.1:p.Asn1722His missense NM_001407652.1:c.5146A>C NP_001394581.1:p.Asn1716His missense NM_001407653.1:c.5146A>C NP_001394582.1:p.Asn1716His missense NM_001407654.1:c.5146A>C NP_001394583.1:p.Asn1716His missense NM_001407655.1:c.5146A>C NP_001394584.1:p.Asn1716His missense NM_001407656.1:c.5143A>C NP_001394585.1:p.Asn1715His missense NM_001407657.1:c.5143A>C NP_001394586.1:p.Asn1715His missense NM_001407658.1:c.5143A>C NP_001394587.1:p.Asn1715His missense NM_001407659.1:c.5140A>C NP_001394588.1:p.Asn1714His missense NM_001407660.1:c.5140A>C NP_001394589.1:p.Asn1714His missense NM_001407661.1:c.5140A>C NP_001394590.1:p.Asn1714His missense NM_001407662.1:c.5140A>C NP_001394591.1:p.Asn1714His missense NM_001407663.1:c.5140A>C NP_001394592.1:p.Asn1714His missense NM_001407664.1:c.5101A>C NP_001394593.1:p.Asn1701His missense NM_001407665.1:c.5101A>C NP_001394594.1:p.Asn1701His missense NM_001407666.1:c.5101A>C NP_001394595.1:p.Asn1701His missense NM_001407667.1:c.5101A>C NP_001394596.1:p.Asn1701His missense NM_001407668.1:c.5101A>C NP_001394597.1:p.Asn1701His missense NM_001407669.1:c.5101A>C NP_001394598.1:p.Asn1701His missense NM_001407670.1:c.5098A>C NP_001394599.1:p.Asn1700His missense NM_001407671.1:c.5098A>C NP_001394600.1:p.Asn1700His missense NM_001407672.1:c.5098A>C NP_001394601.1:p.Asn1700His missense NM_001407673.1:c.5098A>C NP_001394602.1:p.Asn1700His missense NM_001407674.1:c.5098A>C NP_001394603.1:p.Asn1700His missense NM_001407675.1:c.5098A>C NP_001394604.1:p.Asn1700His missense NM_001407676.1:c.5098A>C NP_001394605.1:p.Asn1700His missense NM_001407677.1:c.5098A>C NP_001394606.1:p.Asn1700His missense NM_001407678.1:c.5098A>C NP_001394607.1:p.Asn1700His missense NM_001407679.1:c.5098A>C NP_001394608.1:p.Asn1700His missense NM_001407680.1:c.5098A>C NP_001394609.1:p.Asn1700His missense NM_001407681.1:c.5095A>C NP_001394610.1:p.Asn1699His missense NM_001407682.1:c.5095A>C NP_001394611.1:p.Asn1699His missense NM_001407683.1:c.5095A>C NP_001394612.1:p.Asn1699His missense NM_001407684.1:c.5224A>C NP_001394613.1:p.Asn1742His missense NM_001407685.1:c.5095A>C NP_001394614.1:p.Asn1699His missense NM_001407686.1:c.5095A>C NP_001394615.1:p.Asn1699His missense NM_001407687.1:c.5095A>C NP_001394616.1:p.Asn1699His missense NM_001407688.1:c.5095A>C NP_001394617.1:p.Asn1699His missense NM_001407689.1:c.5095A>C NP_001394618.1:p.Asn1699His missense NM_001407690.1:c.5092A>C NP_001394619.1:p.Asn1698His missense NM_001407691.1:c.5092A>C NP_001394620.1:p.Asn1698His missense NM_001407692.1:c.5083A>C NP_001394621.1:p.Asn1695His missense NM_001407694.1:c.5083A>C NP_001394623.1:p.Asn1695His missense NM_001407695.1:c.5083A>C NP_001394624.1:p.Asn1695His missense NM_001407696.1:c.5083A>C NP_001394625.1:p.Asn1695His missense NM_001407697.1:c.5083A>C NP_001394626.1:p.Asn1695His missense NM_001407698.1:c.5083A>C NP_001394627.1:p.Asn1695His missense NM_001407724.1:c.5083A>C NP_001394653.1:p.Asn1695His missense NM_001407725.1:c.5083A>C NP_001394654.1:p.Asn1695His missense NM_001407726.1:c.5083A>C NP_001394655.1:p.Asn1695His missense NM_001407727.1:c.5083A>C NP_001394656.1:p.Asn1695His missense NM_001407728.1:c.5083A>C NP_001394657.1:p.Asn1695His missense NM_001407729.1:c.5083A>C NP_001394658.1:p.Asn1695His missense NM_001407730.1:c.5083A>C NP_001394659.1:p.Asn1695His missense NM_001407731.1:c.5083A>C NP_001394660.1:p.Asn1695His missense NM_001407732.1:c.5080A>C NP_001394661.1:p.Asn1694His missense NM_001407733.1:c.5080A>C NP_001394662.1:p.Asn1694His missense NM_001407734.1:c.5080A>C NP_001394663.1:p.Asn1694His missense NM_001407735.1:c.5080A>C NP_001394664.1:p.Asn1694His missense NM_001407736.1:c.5080A>C NP_001394665.1:p.Asn1694His missense NM_001407737.1:c.5080A>C NP_001394666.1:p.Asn1694His missense NM_001407738.1:c.5080A>C NP_001394667.1:p.Asn1694His missense NM_001407739.1:c.5080A>C NP_001394668.1:p.Asn1694His missense NM_001407740.1:c.5080A>C NP_001394669.1:p.Asn1694His missense NM_001407741.1:c.5080A>C NP_001394670.1:p.Asn1694His missense NM_001407742.1:c.5080A>C NP_001394671.1:p.Asn1694His missense NM_001407743.1:c.5080A>C NP_001394672.1:p.Asn1694His missense NM_001407744.1:c.5080A>C NP_001394673.1:p.Asn1694His missense NM_001407745.1:c.5080A>C NP_001394674.1:p.Asn1694His missense NM_001407746.1:c.5080A>C NP_001394675.1:p.Asn1694His missense NM_001407747.1:c.5080A>C NP_001394676.1:p.Asn1694His missense NM_001407748.1:c.5080A>C NP_001394677.1:p.Asn1694His missense NM_001407749.1:c.5080A>C NP_001394678.1:p.Asn1694His missense NM_001407750.1:c.5080A>C NP_001394679.1:p.Asn1694His missense NM_001407751.1:c.5080A>C NP_001394680.1:p.Asn1694His missense NM_001407752.1:c.5080A>C NP_001394681.1:p.Asn1694His missense NM_001407838.1:c.5077A>C NP_001394767.1:p.Asn1693His missense NM_001407839.1:c.5077A>C NP_001394768.1:p.Asn1693His missense NM_001407841.1:c.5077A>C NP_001394770.1:p.Asn1693His missense NM_001407842.1:c.5077A>C NP_001394771.1:p.Asn1693His missense NM_001407843.1:c.5077A>C NP_001394772.1:p.Asn1693His missense NM_001407844.1:c.5077A>C NP_001394773.1:p.Asn1693His missense NM_001407845.1:c.5077A>C NP_001394774.1:p.Asn1693His missense NM_001407846.1:c.5077A>C NP_001394775.1:p.Asn1693His missense NM_001407847.1:c.5077A>C NP_001394776.1:p.Asn1693His missense NM_001407848.1:c.5077A>C NP_001394777.1:p.Asn1693His missense NM_001407849.1:c.5077A>C NP_001394778.1:p.Asn1693His missense NM_001407850.1:c.5077A>C NP_001394779.1:p.Asn1693His missense NM_001407851.1:c.5077A>C NP_001394780.1:p.Asn1693His missense NM_001407852.1:c.5077A>C NP_001394781.1:p.Asn1693His missense NM_001407853.1:c.5077A>C NP_001394782.1:p.Asn1693His missense NM_001407854.1:c.5224A>C NP_001394783.1:p.Asn1742His missense NM_001407858.1:c.5221A>C NP_001394787.1:p.Asn1741His missense NM_001407859.1:c.5221A>C NP_001394788.1:p.Asn1741His missense NM_001407860.1:c.5221A>C NP_001394789.1:p.Asn1741His missense NM_001407861.1:c.5218A>C NP_001394790.1:p.Asn1740His missense NM_001407862.1:c.5023A>C NP_001394791.1:p.Asn1675His missense NM_001407863.1:c.5020A>C NP_001394792.1:p.Asn1674His missense NM_001407874.1:c.5017A>C NP_001394803.1:p.Asn1673His missense NM_001407875.1:c.5017A>C NP_001394804.1:p.Asn1673His missense NM_001407879.1:c.5014A>C NP_001394808.1:p.Asn1672His missense NM_001407881.1:c.5014A>C NP_001394810.1:p.Asn1672His missense NM_001407882.1:c.5014A>C NP_001394811.1:p.Asn1672His missense NM_001407884.1:c.5014A>C NP_001394813.1:p.Asn1672His missense NM_001407885.1:c.5014A>C NP_001394814.1:p.Asn1672His missense NM_001407886.1:c.5014A>C NP_001394815.1:p.Asn1672His missense NM_001407887.1:c.5014A>C NP_001394816.1:p.Asn1672His missense NM_001407889.1:c.5014A>C NP_001394818.1:p.Asn1672His missense NM_001407894.1:c.5011A>C NP_001394823.1:p.Asn1671His missense NM_001407895.1:c.5011A>C NP_001394824.1:p.Asn1671His missense NM_001407896.1:c.5011A>C NP_001394825.1:p.Asn1671His missense NM_001407897.1:c.5011A>C NP_001394826.1:p.Asn1671His missense NM_001407898.1:c.5011A>C NP_001394827.1:p.Asn1671His missense NM_001407899.1:c.5011A>C NP_001394828.1:p.Asn1671His missense NM_001407900.1:c.5011A>C NP_001394829.1:p.Asn1671His missense NM_001407902.1:c.5011A>C NP_001394831.1:p.Asn1671His missense NM_001407904.1:c.5011A>C NP_001394833.1:p.Asn1671His missense NM_001407906.1:c.5011A>C NP_001394835.1:p.Asn1671His missense NM_001407907.1:c.5011A>C NP_001394836.1:p.Asn1671His missense NM_001407908.1:c.5011A>C NP_001394837.1:p.Asn1671His missense NM_001407909.1:c.5011A>C NP_001394838.1:p.Asn1671His missense NM_001407910.1:c.5011A>C NP_001394839.1:p.Asn1671His missense NM_001407915.1:c.5008A>C NP_001394844.1:p.Asn1670His missense NM_001407916.1:c.5008A>C NP_001394845.1:p.Asn1670His missense NM_001407917.1:c.5008A>C NP_001394846.1:p.Asn1670His missense NM_001407918.1:c.5008A>C NP_001394847.1:p.Asn1670His missense NM_001407919.1:c.5101A>C NP_001394848.1:p.Asn1701His missense NM_001407920.1:c.4960A>C NP_001394849.1:p.Asn1654His missense NM_001407921.1:c.4960A>C NP_001394850.1:p.Asn1654His missense NM_001407922.1:c.4960A>C NP_001394851.1:p.Asn1654His missense NM_001407923.1:c.4960A>C NP_001394852.1:p.Asn1654His missense NM_001407924.1:c.4960A>C NP_001394853.1:p.Asn1654His missense NM_001407925.1:c.4960A>C NP_001394854.1:p.Asn1654His missense NM_001407926.1:c.4960A>C NP_001394855.1:p.Asn1654His missense NM_001407927.1:c.4957A>C NP_001394856.1:p.Asn1653His missense NM_001407928.1:c.4957A>C NP_001394857.1:p.Asn1653His missense NM_001407929.1:c.4957A>C NP_001394858.1:p.Asn1653His missense NM_001407930.1:c.4957A>C NP_001394859.1:p.Asn1653His missense NM_001407931.1:c.4957A>C NP_001394860.1:p.Asn1653His missense NM_001407932.1:c.4957A>C NP_001394861.1:p.Asn1653His missense NM_001407933.1:c.4957A>C NP_001394862.1:p.Asn1653His missense NM_001407934.1:c.4954A>C NP_001394863.1:p.Asn1652His missense NM_001407935.1:c.4954A>C NP_001394864.1:p.Asn1652His missense NM_001407936.1:c.4954A>C NP_001394865.1:p.Asn1652His missense NM_001407937.1:c.5101A>C NP_001394866.1:p.Asn1701His missense NM_001407938.1:c.5101A>C NP_001394867.1:p.Asn1701His missense NM_001407939.1:c.5098A>C NP_001394868.1:p.Asn1700His missense NM_001407940.1:c.5098A>C NP_001394869.1:p.Asn1700His missense NM_001407941.1:c.5095A>C NP_001394870.1:p.Asn1699His missense NM_001407942.1:c.5083A>C NP_001394871.1:p.Asn1695His missense NM_001407943.1:c.5080A>C NP_001394872.1:p.Asn1694His missense NM_001407944.1:c.5080A>C NP_001394873.1:p.Asn1694His missense NM_001407945.1:c.5080A>C NP_001394874.1:p.Asn1694His missense NM_001407946.1:c.4891A>C NP_001394875.1:p.Asn1631His missense NM_001407947.1:c.4891A>C NP_001394876.1:p.Asn1631His missense NM_001407948.1:c.4891A>C NP_001394877.1:p.Asn1631His missense NM_001407949.1:c.4891A>C NP_001394878.1:p.Asn1631His missense NM_001407950.1:c.4888A>C NP_001394879.1:p.Asn1630His missense NM_001407951.1:c.4888A>C NP_001394880.1:p.Asn1630His missense NM_001407952.1:c.4888A>C NP_001394881.1:p.Asn1630His missense NM_001407953.1:c.4888A>C NP_001394882.1:p.Asn1630His missense NM_001407954.1:c.4888A>C NP_001394883.1:p.Asn1630His missense NM_001407955.1:c.4888A>C NP_001394884.1:p.Asn1630His missense NM_001407956.1:c.4885A>C NP_001394885.1:p.Asn1629His missense NM_001407957.1:c.4885A>C NP_001394886.1:p.Asn1629His missense NM_001407958.1:c.4885A>C NP_001394887.1:p.Asn1629His missense NM_001407959.1:c.4843A>C NP_001394888.1:p.Asn1615His missense NM_001407960.1:c.4840A>C NP_001394889.1:p.Asn1614His missense NM_001407962.1:c.4840A>C NP_001394891.1:p.Asn1614His missense NM_001407963.1:c.4837A>C NP_001394892.1:p.Asn1613His missense NM_001407964.1:c.4762A>C NP_001394893.1:p.Asn1588His missense NM_001407965.1:c.4717A>C NP_001394894.1:p.Asn1573His missense NM_001407966.1:c.4336A>C NP_001394895.1:p.Asn1446His missense NM_001407967.1:c.4333A>C NP_001394896.1:p.Asn1445His missense NM_001407968.1:c.2620A>C NP_001394897.1:p.Asn874His missense NM_001407969.1:c.2617A>C NP_001394898.1:p.Asn873His missense NM_001407970.1:c.1981A>C NP_001394899.1:p.Asn661His missense NM_001407971.1:c.1981A>C NP_001394900.1:p.Asn661His missense NM_001407972.1:c.1978A>C NP_001394901.1:p.Asn660His missense NM_001407973.1:c.1915A>C NP_001394902.1:p.Asn639His missense NM_001407974.1:c.1915A>C NP_001394903.1:p.Asn639His missense NM_001407975.1:c.1915A>C NP_001394904.1:p.Asn639His missense NM_001407976.1:c.1915A>C NP_001394905.1:p.Asn639His missense NM_001407977.1:c.1915A>C NP_001394906.1:p.Asn639His missense NM_001407978.1:c.1915A>C NP_001394907.1:p.Asn639His missense NM_001407979.1:c.1912A>C NP_001394908.1:p.Asn638His missense NM_001407980.1:c.1912A>C NP_001394909.1:p.Asn638His missense NM_001407981.1:c.1912A>C NP_001394910.1:p.Asn638His missense NM_001407982.1:c.1912A>C NP_001394911.1:p.Asn638His missense NM_001407983.1:c.1912A>C NP_001394912.1:p.Asn638His missense NM_001407984.1:c.1912A>C NP_001394913.1:p.Asn638His missense NM_001407985.1:c.1912A>C NP_001394914.1:p.Asn638His missense NM_001407986.1:c.1912A>C NP_001394915.1:p.Asn638His missense NM_001407990.1:c.1912A>C NP_001394919.1:p.Asn638His missense NM_001407991.1:c.1912A>C NP_001394920.1:p.Asn638His missense NM_001407992.1:c.1912A>C NP_001394921.1:p.Asn638His missense NM_001407993.1:c.1912A>C NP_001394922.1:p.Asn638His missense NM_001408392.1:c.1909A>C NP_001395321.1:p.Asn637His missense NM_001408396.1:c.1909A>C NP_001395325.1:p.Asn637His missense NM_001408397.1:c.1909A>C NP_001395326.1:p.Asn637His missense NM_001408398.1:c.1909A>C NP_001395327.1:p.Asn637His missense NM_001408399.1:c.1909A>C NP_001395328.1:p.Asn637His missense NM_001408400.1:c.1909A>C NP_001395329.1:p.Asn637His missense NM_001408401.1:c.1909A>C NP_001395330.1:p.Asn637His missense NM_001408402.1:c.1909A>C NP_001395331.1:p.Asn637His missense NM_001408403.1:c.1909A>C NP_001395332.1:p.Asn637His missense NM_001408404.1:c.1909A>C NP_001395333.1:p.Asn637His missense NM_001408406.1:c.1906A>C NP_001395335.1:p.Asn636His missense NM_001408407.1:c.1906A>C NP_001395336.1:p.Asn636His missense NM_001408408.1:c.1906A>C NP_001395337.1:p.Asn636His missense NM_001408409.1:c.1903A>C NP_001395338.1:p.Asn635His missense NM_001408410.1:c.1840A>C NP_001395339.1:p.Asn614His missense NM_001408411.1:c.1837A>C NP_001395340.1:p.Asn613His missense NM_001408412.1:c.1834A>C NP_001395341.1:p.Asn612His missense NM_001408413.1:c.1834A>C NP_001395342.1:p.Asn612His missense NM_001408414.1:c.1834A>C NP_001395343.1:p.Asn612His missense NM_001408415.1:c.1834A>C NP_001395344.1:p.Asn612His missense NM_001408416.1:c.1834A>C NP_001395345.1:p.Asn612His missense NM_001408418.1:c.1798A>C NP_001395347.1:p.Asn600His missense NM_001408419.1:c.1798A>C NP_001395348.1:p.Asn600His missense NM_001408420.1:c.1798A>C NP_001395349.1:p.Asn600His missense NM_001408421.1:c.1795A>C NP_001395350.1:p.Asn599His missense NM_001408422.1:c.1795A>C NP_001395351.1:p.Asn599His missense NM_001408423.1:c.1795A>C NP_001395352.1:p.Asn599His missense NM_001408424.1:c.1795A>C NP_001395353.1:p.Asn599His missense NM_001408425.1:c.1792A>C NP_001395354.1:p.Asn598His missense NM_001408426.1:c.1792A>C NP_001395355.1:p.Asn598His missense NM_001408427.1:c.1792A>C NP_001395356.1:p.Asn598His missense NM_001408428.1:c.1792A>C NP_001395357.1:p.Asn598His missense NM_001408429.1:c.1792A>C NP_001395358.1:p.Asn598His missense NM_001408430.1:c.1792A>C NP_001395359.1:p.Asn598His missense NM_001408431.1:c.1792A>C NP_001395360.1:p.Asn598His missense NM_001408432.1:c.1789A>C NP_001395361.1:p.Asn597His missense NM_001408433.1:c.1789A>C NP_001395362.1:p.Asn597His missense NM_001408434.1:c.1789A>C NP_001395363.1:p.Asn597His missense NM_001408435.1:c.1789A>C NP_001395364.1:p.Asn597His missense NM_001408436.1:c.1789A>C NP_001395365.1:p.Asn597His missense NM_001408437.1:c.1789A>C NP_001395366.1:p.Asn597His missense NM_001408438.1:c.1789A>C NP_001395367.1:p.Asn597His missense NM_001408439.1:c.1789A>C NP_001395368.1:p.Asn597His missense NM_001408440.1:c.1789A>C NP_001395369.1:p.Asn597His missense NM_001408441.1:c.1789A>C NP_001395370.1:p.Asn597His missense NM_001408442.1:c.1789A>C NP_001395371.1:p.Asn597His missense NM_001408443.1:c.1789A>C NP_001395372.1:p.Asn597His missense NM_001408444.1:c.1789A>C NP_001395373.1:p.Asn597His missense NM_001408445.1:c.1786A>C NP_001395374.1:p.Asn596His missense NM_001408446.1:c.1786A>C NP_001395375.1:p.Asn596His missense NM_001408447.1:c.1786A>C NP_001395376.1:p.Asn596His missense NM_001408448.1:c.1786A>C NP_001395377.1:p.Asn596His missense NM_001408450.1:c.1786A>C NP_001395379.1:p.Asn596His missense NM_001408451.1:c.1780A>C NP_001395380.1:p.Asn594His missense NM_001408452.1:c.1774A>C NP_001395381.1:p.Asn592His missense NM_001408453.1:c.1774A>C NP_001395382.1:p.Asn592His missense NM_001408454.1:c.1774A>C NP_001395383.1:p.Asn592His missense NM_001408455.1:c.1774A>C NP_001395384.1:p.Asn592His missense NM_001408456.1:c.1774A>C NP_001395385.1:p.Asn592His missense NM_001408457.1:c.1774A>C NP_001395386.1:p.Asn592His missense NM_001408458.1:c.1771A>C NP_001395387.1:p.Asn591His missense NM_001408459.1:c.1771A>C NP_001395388.1:p.Asn591His missense NM_001408460.1:c.1771A>C NP_001395389.1:p.Asn591His missense NM_001408461.1:c.1771A>C NP_001395390.1:p.Asn591His missense NM_001408462.1:c.1771A>C NP_001395391.1:p.Asn591His missense NM_001408463.1:c.1771A>C NP_001395392.1:p.Asn591His missense NM_001408464.1:c.1771A>C NP_001395393.1:p.Asn591His missense NM_001408465.1:c.1771A>C NP_001395394.1:p.Asn591His missense NM_001408466.1:c.1771A>C NP_001395395.1:p.Asn591His missense NM_001408467.1:c.1771A>C NP_001395396.1:p.Asn591His missense NM_001408468.1:c.1768A>C NP_001395397.1:p.Asn590His missense NM_001408469.1:c.1768A>C NP_001395398.1:p.Asn590His missense NM_001408470.1:c.1768A>C NP_001395399.1:p.Asn590His missense NM_001408472.1:c.1912A>C NP_001395401.1:p.Asn638His missense NM_001408473.1:c.1909A>C NP_001395402.1:p.Asn637His missense NM_001408474.1:c.1714A>C NP_001395403.1:p.Asn572His missense NM_001408475.1:c.1711A>C NP_001395404.1:p.Asn571His missense NM_001408476.1:c.1711A>C NP_001395405.1:p.Asn571His missense NM_001408478.1:c.1705A>C NP_001395407.1:p.Asn569His missense NM_001408479.1:c.1705A>C NP_001395408.1:p.Asn569His missense NM_001408480.1:c.1705A>C NP_001395409.1:p.Asn569His missense NM_001408481.1:c.1702A>C NP_001395410.1:p.Asn568His missense NM_001408482.1:c.1702A>C NP_001395411.1:p.Asn568His missense NM_001408483.1:c.1702A>C NP_001395412.1:p.Asn568His missense NM_001408484.1:c.1702A>C NP_001395413.1:p.Asn568His missense NM_001408485.1:c.1702A>C NP_001395414.1:p.Asn568His missense NM_001408489.1:c.1702A>C NP_001395418.1:p.Asn568His missense NM_001408490.1:c.1702A>C NP_001395419.1:p.Asn568His missense NM_001408491.1:c.1702A>C NP_001395420.1:p.Asn568His missense NM_001408492.1:c.1699A>C NP_001395421.1:p.Asn567His missense NM_001408493.1:c.1699A>C NP_001395422.1:p.Asn567His missense NM_001408494.1:c.1675A>C NP_001395423.1:p.Asn559His missense NM_001408495.1:c.1669A>C NP_001395424.1:p.Asn557His missense NM_001408496.1:c.1651A>C NP_001395425.1:p.Asn551His missense NM_001408497.1:c.1651A>C NP_001395426.1:p.Asn551His missense NM_001408498.1:c.1651A>C NP_001395427.1:p.Asn551His missense NM_001408499.1:c.1651A>C NP_001395428.1:p.Asn551His missense NM_001408500.1:c.1651A>C NP_001395429.1:p.Asn551His missense NM_001408501.1:c.1651A>C NP_001395430.1:p.Asn551His missense NM_001408502.1:c.1648A>C NP_001395431.1:p.Asn550His missense NM_001408503.1:c.1648A>C NP_001395432.1:p.Asn550His missense NM_001408504.1:c.1648A>C NP_001395433.1:p.Asn550His missense NM_001408505.1:c.1645A>C NP_001395434.1:p.Asn549His missense NM_001408506.1:c.1588A>C NP_001395435.1:p.Asn530His missense NM_001408507.1:c.1585A>C NP_001395436.1:p.Asn529His missense NM_001408508.1:c.1576A>C NP_001395437.1:p.Asn526His missense NM_001408509.1:c.1573A>C NP_001395438.1:p.Asn525His missense NM_001408510.1:c.1534A>C NP_001395439.1:p.Asn512His missense NM_001408511.1:c.1531A>C NP_001395440.1:p.Asn511His missense NM_001408512.1:c.1411A>C NP_001395441.1:p.Asn471His missense NM_001408513.1:c.1384A>C NP_001395442.1:p.Asn462His missense NM_001408514.1:c.988A>C NP_001395443.1:p.Asn330His missense NM_007297.4:c.5083A>C NP_009228.2:p.Asn1695His missense NM_007298.4:c.1912A>C NP_009229.2:p.Asn638His missense NM_007299.4:c.1912A>C NP_009230.2:p.Asn638His missense NM_007300.4:c.5287A>C NP_009231.2:p.Asn1763His missense NM_007304.2:c.1912A>C NP_009235.2:p.Asn638His missense NR_027676.2:n.5401A>C non-coding transcript variant NC_000017.11:g.43057105T>G NC_000017.10:g.41209122T>G NG_005905.2:g.160879A>C LRG_292:g.160879A>C LRG_292t1:c.5224A>C LRG_292p1:p.Asn1742His - Protein change
- N1742H, N638H, N1763H, N1695H, N1445H, N1446H, N1588H, N1615H, N1652H, N1670H, N1671H, N1698H, N1699H, N1700H, N1739H, N1741H, N530H, N550H, N559H, N567H, N594H, N597H, N599H, N613H, N635H, N637H, N1630H, N1631H, N1653H, N1672H, N1673H, N1715H, N1762H, N462H, N511H, N512H, N526H, N549H, N571H, N590H, N596H, N600H, N614H, N636H, N639H, N661H, N1613H, N1654H, N1693H, N1694H, N1701H, N1722H, N1737H, N1764H, N330H, N471H, N525H, N551H, N557H, N572H, N598H, N612H, N660H, N874H, N1573H, N1614H, N1629H, N1674H, N1675H, N1714H, N1716H, N1723H, N1738H, N1740H, N529H, N568H, N569H, N591H, N592H, N873H
- Other names
- -
- Canonical SPDI
- NC_000017.11:43057104:T:G
-
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.5224A>C, a MISSENSE variant, produced a function score of -0.03, 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.
- -
- 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
|
- | RCV001077049.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
May 9, 2023 | RCV001225940.8 |
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
(May 09, 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: SCV001398234.5
First in ClinVar: Jul 16, 2020 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 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. ClinVar contains an entry for this variant (Variation ID: 868199). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1742 of the BRCA1 protein (p.Asn1742His). (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: SCV001242912.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.0283156120907143
|
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_normal
|
Method citation(s):
|
|
Brotman Baty Institute, University of Washington
Accession: SCV001242912.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5224A>C, a MISSENSE variant, produced a function score of -0.03, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5224A>C, a MISSENSE variant, produced a function score of -0.03, 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 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. ClinVar contains an entry for this variant (Variation ID: 868199). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1742 of the BRCA1 protein (p.Asn1742His).
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 rs1597810828 ...
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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.