This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1732 of the BRCA1 protein (p.His1732Asn). 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). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 867500). 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).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5194C>A (p.His1732Asn)
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.5194C>A (p.His1732Asn)
Variation ID: 867500 Accession: VCV000867500.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43057135 (GRCh38) [ NCBI UCSC ] 17: 41209152 (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 Jun 21, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5194C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.His1732Asn missense NM_001407571.1:c.4981C>A NP_001394500.1:p.His1661Asn missense NM_001407581.1:c.5260C>A NP_001394510.1:p.His1754Asn missense NM_001407582.1:c.5260C>A NP_001394511.1:p.His1754Asn missense NM_001407583.1:c.5257C>A NP_001394512.1:p.His1753Asn missense NM_001407585.1:c.5257C>A NP_001394514.1:p.His1753Asn missense NM_001407587.1:c.5257C>A NP_001394516.1:p.His1753Asn missense NM_001407590.1:c.5254C>A NP_001394519.1:p.His1752Asn missense NM_001407591.1:c.5254C>A NP_001394520.1:p.His1752Asn missense NM_001407593.1:c.5194C>A NP_001394522.1:p.His1732Asn missense NM_001407594.1:c.5194C>A NP_001394523.1:p.His1732Asn missense NM_001407596.1:c.5194C>A NP_001394525.1:p.His1732Asn missense NM_001407597.1:c.5194C>A NP_001394526.1:p.His1732Asn missense NM_001407598.1:c.5194C>A NP_001394527.1:p.His1732Asn missense NM_001407602.1:c.5194C>A NP_001394531.1:p.His1732Asn missense NM_001407603.1:c.5194C>A NP_001394532.1:p.His1732Asn missense NM_001407605.1:c.5194C>A NP_001394534.1:p.His1732Asn missense NM_001407610.1:c.5191C>A NP_001394539.1:p.His1731Asn missense NM_001407611.1:c.5191C>A NP_001394540.1:p.His1731Asn missense NM_001407612.1:c.5191C>A NP_001394541.1:p.His1731Asn missense NM_001407613.1:c.5191C>A NP_001394542.1:p.His1731Asn missense NM_001407614.1:c.5191C>A NP_001394543.1:p.His1731Asn missense NM_001407615.1:c.5191C>A NP_001394544.1:p.His1731Asn missense NM_001407616.1:c.5191C>A NP_001394545.1:p.His1731Asn missense NM_001407617.1:c.5191C>A NP_001394546.1:p.His1731Asn missense NM_001407618.1:c.5191C>A NP_001394547.1:p.His1731Asn missense NM_001407619.1:c.5191C>A NP_001394548.1:p.His1731Asn missense NM_001407620.1:c.5191C>A NP_001394549.1:p.His1731Asn missense NM_001407621.1:c.5191C>A NP_001394550.1:p.His1731Asn missense NM_001407622.1:c.5191C>A NP_001394551.1:p.His1731Asn missense NM_001407623.1:c.5191C>A NP_001394552.1:p.His1731Asn missense NM_001407624.1:c.5191C>A NP_001394553.1:p.His1731Asn missense NM_001407625.1:c.5191C>A NP_001394554.1:p.His1731Asn missense NM_001407626.1:c.5191C>A NP_001394555.1:p.His1731Asn missense NM_001407627.1:c.5188C>A NP_001394556.1:p.His1730Asn missense NM_001407628.1:c.5188C>A NP_001394557.1:p.His1730Asn missense NM_001407629.1:c.5188C>A NP_001394558.1:p.His1730Asn missense NM_001407630.1:c.5188C>A NP_001394559.1:p.His1730Asn missense NM_001407631.1:c.5188C>A NP_001394560.1:p.His1730Asn missense NM_001407632.1:c.5188C>A NP_001394561.1:p.His1730Asn missense NM_001407633.1:c.5188C>A NP_001394562.1:p.His1730Asn missense NM_001407634.1:c.5188C>A NP_001394563.1:p.His1730Asn missense NM_001407635.1:c.5188C>A NP_001394564.1:p.His1730Asn missense NM_001407636.1:c.5188C>A NP_001394565.1:p.His1730Asn missense NM_001407637.1:c.5188C>A NP_001394566.1:p.His1730Asn missense NM_001407638.1:c.5188C>A NP_001394567.1:p.His1730Asn missense NM_001407639.1:c.5188C>A NP_001394568.1:p.His1730Asn missense NM_001407640.1:c.5188C>A NP_001394569.1:p.His1730Asn missense NM_001407641.1:c.5188C>A NP_001394570.1:p.His1730Asn missense NM_001407642.1:c.5188C>A NP_001394571.1:p.His1730Asn missense NM_001407644.1:c.5185C>A NP_001394573.1:p.His1729Asn missense NM_001407645.1:c.5185C>A NP_001394574.1:p.His1729Asn missense NM_001407646.1:c.5182C>A NP_001394575.1:p.His1728Asn missense NM_001407647.1:c.5179C>A NP_001394576.1:p.His1727Asn missense NM_001407648.1:c.5137C>A NP_001394577.1:p.His1713Asn missense NM_001407649.1:c.5134C>A NP_001394578.1:p.His1712Asn missense NM_001407652.1:c.5116C>A NP_001394581.1:p.His1706Asn missense NM_001407653.1:c.5116C>A NP_001394582.1:p.His1706Asn missense NM_001407654.1:c.5116C>A NP_001394583.1:p.His1706Asn missense NM_001407655.1:c.5116C>A NP_001394584.1:p.His1706Asn missense NM_001407656.1:c.5113C>A NP_001394585.1:p.His1705Asn missense NM_001407657.1:c.5113C>A NP_001394586.1:p.His1705Asn missense NM_001407658.1:c.5113C>A NP_001394587.1:p.His1705Asn missense NM_001407659.1:c.5110C>A NP_001394588.1:p.His1704Asn missense NM_001407660.1:c.5110C>A NP_001394589.1:p.His1704Asn missense NM_001407661.1:c.5110C>A NP_001394590.1:p.His1704Asn missense NM_001407662.1:c.5110C>A NP_001394591.1:p.His1704Asn missense NM_001407663.1:c.5110C>A NP_001394592.1:p.His1704Asn missense NM_001407664.1:c.5071C>A NP_001394593.1:p.His1691Asn missense NM_001407665.1:c.5071C>A NP_001394594.1:p.His1691Asn missense NM_001407666.1:c.5071C>A NP_001394595.1:p.His1691Asn missense NM_001407667.1:c.5071C>A NP_001394596.1:p.His1691Asn missense NM_001407668.1:c.5071C>A NP_001394597.1:p.His1691Asn missense NM_001407669.1:c.5071C>A NP_001394598.1:p.His1691Asn missense NM_001407670.1:c.5068C>A NP_001394599.1:p.His1690Asn missense NM_001407671.1:c.5068C>A NP_001394600.1:p.His1690Asn missense NM_001407672.1:c.5068C>A NP_001394601.1:p.His1690Asn missense NM_001407673.1:c.5068C>A NP_001394602.1:p.His1690Asn missense NM_001407674.1:c.5068C>A NP_001394603.1:p.His1690Asn missense NM_001407675.1:c.5068C>A NP_001394604.1:p.His1690Asn missense NM_001407676.1:c.5068C>A NP_001394605.1:p.His1690Asn missense NM_001407677.1:c.5068C>A NP_001394606.1:p.His1690Asn missense NM_001407678.1:c.5068C>A NP_001394607.1:p.His1690Asn missense NM_001407679.1:c.5068C>A NP_001394608.1:p.His1690Asn missense NM_001407680.1:c.5068C>A NP_001394609.1:p.His1690Asn missense NM_001407681.1:c.5065C>A NP_001394610.1:p.His1689Asn missense NM_001407682.1:c.5065C>A NP_001394611.1:p.His1689Asn missense NM_001407683.1:c.5065C>A NP_001394612.1:p.His1689Asn missense NM_001407684.1:c.5194C>A NP_001394613.1:p.His1732Asn missense NM_001407685.1:c.5065C>A NP_001394614.1:p.His1689Asn missense NM_001407686.1:c.5065C>A NP_001394615.1:p.His1689Asn missense NM_001407687.1:c.5065C>A NP_001394616.1:p.His1689Asn missense NM_001407688.1:c.5065C>A NP_001394617.1:p.His1689Asn missense NM_001407689.1:c.5065C>A NP_001394618.1:p.His1689Asn missense NM_001407690.1:c.5062C>A NP_001394619.1:p.His1688Asn missense NM_001407691.1:c.5062C>A NP_001394620.1:p.His1688Asn missense NM_001407692.1:c.5053C>A NP_001394621.1:p.His1685Asn missense NM_001407694.1:c.5053C>A NP_001394623.1:p.His1685Asn missense NM_001407695.1:c.5053C>A NP_001394624.1:p.His1685Asn missense NM_001407696.1:c.5053C>A NP_001394625.1:p.His1685Asn missense NM_001407697.1:c.5053C>A NP_001394626.1:p.His1685Asn missense NM_001407698.1:c.5053C>A NP_001394627.1:p.His1685Asn missense NM_001407724.1:c.5053C>A NP_001394653.1:p.His1685Asn missense NM_001407725.1:c.5053C>A NP_001394654.1:p.His1685Asn missense NM_001407726.1:c.5053C>A NP_001394655.1:p.His1685Asn missense NM_001407727.1:c.5053C>A NP_001394656.1:p.His1685Asn missense NM_001407728.1:c.5053C>A NP_001394657.1:p.His1685Asn missense NM_001407729.1:c.5053C>A NP_001394658.1:p.His1685Asn missense NM_001407730.1:c.5053C>A NP_001394659.1:p.His1685Asn missense NM_001407731.1:c.5053C>A NP_001394660.1:p.His1685Asn missense NM_001407732.1:c.5050C>A NP_001394661.1:p.His1684Asn missense NM_001407733.1:c.5050C>A NP_001394662.1:p.His1684Asn missense NM_001407734.1:c.5050C>A NP_001394663.1:p.His1684Asn missense NM_001407735.1:c.5050C>A NP_001394664.1:p.His1684Asn missense NM_001407736.1:c.5050C>A NP_001394665.1:p.His1684Asn missense NM_001407737.1:c.5050C>A NP_001394666.1:p.His1684Asn missense NM_001407738.1:c.5050C>A NP_001394667.1:p.His1684Asn missense NM_001407739.1:c.5050C>A NP_001394668.1:p.His1684Asn missense NM_001407740.1:c.5050C>A NP_001394669.1:p.His1684Asn missense NM_001407741.1:c.5050C>A NP_001394670.1:p.His1684Asn missense NM_001407742.1:c.5050C>A NP_001394671.1:p.His1684Asn missense NM_001407743.1:c.5050C>A NP_001394672.1:p.His1684Asn missense NM_001407744.1:c.5050C>A NP_001394673.1:p.His1684Asn missense NM_001407745.1:c.5050C>A NP_001394674.1:p.His1684Asn missense NM_001407746.1:c.5050C>A NP_001394675.1:p.His1684Asn missense NM_001407747.1:c.5050C>A NP_001394676.1:p.His1684Asn missense NM_001407748.1:c.5050C>A NP_001394677.1:p.His1684Asn missense NM_001407749.1:c.5050C>A NP_001394678.1:p.His1684Asn missense NM_001407750.1:c.5050C>A NP_001394679.1:p.His1684Asn missense NM_001407751.1:c.5050C>A NP_001394680.1:p.His1684Asn missense NM_001407752.1:c.5050C>A NP_001394681.1:p.His1684Asn missense NM_001407838.1:c.5047C>A NP_001394767.1:p.His1683Asn missense NM_001407839.1:c.5047C>A NP_001394768.1:p.His1683Asn missense NM_001407841.1:c.5047C>A NP_001394770.1:p.His1683Asn missense NM_001407842.1:c.5047C>A NP_001394771.1:p.His1683Asn missense NM_001407843.1:c.5047C>A NP_001394772.1:p.His1683Asn missense NM_001407844.1:c.5047C>A NP_001394773.1:p.His1683Asn missense NM_001407845.1:c.5047C>A NP_001394774.1:p.His1683Asn missense NM_001407846.1:c.5047C>A NP_001394775.1:p.His1683Asn missense NM_001407847.1:c.5047C>A NP_001394776.1:p.His1683Asn missense NM_001407848.1:c.5047C>A NP_001394777.1:p.His1683Asn missense NM_001407849.1:c.5047C>A NP_001394778.1:p.His1683Asn missense NM_001407850.1:c.5047C>A NP_001394779.1:p.His1683Asn missense NM_001407851.1:c.5047C>A NP_001394780.1:p.His1683Asn missense NM_001407852.1:c.5047C>A NP_001394781.1:p.His1683Asn missense NM_001407853.1:c.5047C>A NP_001394782.1:p.His1683Asn missense NM_001407854.1:c.5194C>A NP_001394783.1:p.His1732Asn missense NM_001407858.1:c.5191C>A NP_001394787.1:p.His1731Asn missense NM_001407859.1:c.5191C>A NP_001394788.1:p.His1731Asn missense NM_001407860.1:c.5191C>A NP_001394789.1:p.His1731Asn missense NM_001407861.1:c.5188C>A NP_001394790.1:p.His1730Asn missense NM_001407862.1:c.4993C>A NP_001394791.1:p.His1665Asn missense NM_001407863.1:c.4990C>A NP_001394792.1:p.His1664Asn missense NM_001407874.1:c.4987C>A NP_001394803.1:p.His1663Asn missense NM_001407875.1:c.4987C>A NP_001394804.1:p.His1663Asn missense NM_001407879.1:c.4984C>A NP_001394808.1:p.His1662Asn missense NM_001407881.1:c.4984C>A NP_001394810.1:p.His1662Asn missense NM_001407882.1:c.4984C>A NP_001394811.1:p.His1662Asn missense NM_001407884.1:c.4984C>A NP_001394813.1:p.His1662Asn missense NM_001407885.1:c.4984C>A NP_001394814.1:p.His1662Asn missense NM_001407886.1:c.4984C>A NP_001394815.1:p.His1662Asn missense NM_001407887.1:c.4984C>A NP_001394816.1:p.His1662Asn missense NM_001407889.1:c.4984C>A NP_001394818.1:p.His1662Asn missense NM_001407894.1:c.4981C>A NP_001394823.1:p.His1661Asn missense NM_001407895.1:c.4981C>A NP_001394824.1:p.His1661Asn missense NM_001407896.1:c.4981C>A NP_001394825.1:p.His1661Asn missense NM_001407897.1:c.4981C>A NP_001394826.1:p.His1661Asn missense NM_001407898.1:c.4981C>A NP_001394827.1:p.His1661Asn missense NM_001407899.1:c.4981C>A NP_001394828.1:p.His1661Asn missense NM_001407900.1:c.4981C>A NP_001394829.1:p.His1661Asn missense NM_001407902.1:c.4981C>A NP_001394831.1:p.His1661Asn missense NM_001407904.1:c.4981C>A NP_001394833.1:p.His1661Asn missense NM_001407906.1:c.4981C>A NP_001394835.1:p.His1661Asn missense NM_001407907.1:c.4981C>A NP_001394836.1:p.His1661Asn missense NM_001407908.1:c.4981C>A NP_001394837.1:p.His1661Asn missense NM_001407909.1:c.4981C>A NP_001394838.1:p.His1661Asn missense NM_001407910.1:c.4981C>A NP_001394839.1:p.His1661Asn missense NM_001407915.1:c.4978C>A NP_001394844.1:p.His1660Asn missense NM_001407916.1:c.4978C>A NP_001394845.1:p.His1660Asn missense NM_001407917.1:c.4978C>A NP_001394846.1:p.His1660Asn missense NM_001407918.1:c.4978C>A NP_001394847.1:p.His1660Asn missense NM_001407919.1:c.5071C>A NP_001394848.1:p.His1691Asn missense NM_001407920.1:c.4930C>A NP_001394849.1:p.His1644Asn missense NM_001407921.1:c.4930C>A NP_001394850.1:p.His1644Asn missense NM_001407922.1:c.4930C>A NP_001394851.1:p.His1644Asn missense NM_001407923.1:c.4930C>A NP_001394852.1:p.His1644Asn missense NM_001407924.1:c.4930C>A NP_001394853.1:p.His1644Asn missense NM_001407925.1:c.4930C>A NP_001394854.1:p.His1644Asn missense NM_001407926.1:c.4930C>A NP_001394855.1:p.His1644Asn missense NM_001407927.1:c.4927C>A NP_001394856.1:p.His1643Asn missense NM_001407928.1:c.4927C>A NP_001394857.1:p.His1643Asn missense NM_001407929.1:c.4927C>A NP_001394858.1:p.His1643Asn missense NM_001407930.1:c.4927C>A NP_001394859.1:p.His1643Asn missense NM_001407931.1:c.4927C>A NP_001394860.1:p.His1643Asn missense NM_001407932.1:c.4927C>A NP_001394861.1:p.His1643Asn missense NM_001407933.1:c.4927C>A NP_001394862.1:p.His1643Asn missense NM_001407934.1:c.4924C>A NP_001394863.1:p.His1642Asn missense NM_001407935.1:c.4924C>A NP_001394864.1:p.His1642Asn missense NM_001407936.1:c.4924C>A NP_001394865.1:p.His1642Asn missense NM_001407937.1:c.5071C>A NP_001394866.1:p.His1691Asn missense NM_001407938.1:c.5071C>A NP_001394867.1:p.His1691Asn missense NM_001407939.1:c.5068C>A NP_001394868.1:p.His1690Asn missense NM_001407940.1:c.5068C>A NP_001394869.1:p.His1690Asn missense NM_001407941.1:c.5065C>A NP_001394870.1:p.His1689Asn missense NM_001407942.1:c.5053C>A NP_001394871.1:p.His1685Asn missense NM_001407943.1:c.5050C>A NP_001394872.1:p.His1684Asn missense NM_001407944.1:c.5050C>A NP_001394873.1:p.His1684Asn missense NM_001407945.1:c.5050C>A NP_001394874.1:p.His1684Asn missense NM_001407946.1:c.4861C>A NP_001394875.1:p.His1621Asn missense NM_001407947.1:c.4861C>A NP_001394876.1:p.His1621Asn missense NM_001407948.1:c.4861C>A NP_001394877.1:p.His1621Asn missense NM_001407949.1:c.4861C>A NP_001394878.1:p.His1621Asn missense NM_001407950.1:c.4858C>A NP_001394879.1:p.His1620Asn missense NM_001407951.1:c.4858C>A NP_001394880.1:p.His1620Asn missense NM_001407952.1:c.4858C>A NP_001394881.1:p.His1620Asn missense NM_001407953.1:c.4858C>A NP_001394882.1:p.His1620Asn missense NM_001407954.1:c.4858C>A NP_001394883.1:p.His1620Asn missense NM_001407955.1:c.4858C>A NP_001394884.1:p.His1620Asn missense NM_001407956.1:c.4855C>A NP_001394885.1:p.His1619Asn missense NM_001407957.1:c.4855C>A NP_001394886.1:p.His1619Asn missense NM_001407958.1:c.4855C>A NP_001394887.1:p.His1619Asn missense NM_001407959.1:c.4813C>A NP_001394888.1:p.His1605Asn missense NM_001407960.1:c.4810C>A NP_001394889.1:p.His1604Asn missense NM_001407962.1:c.4810C>A NP_001394891.1:p.His1604Asn missense NM_001407963.1:c.4807C>A NP_001394892.1:p.His1603Asn missense NM_001407964.1:c.4732C>A NP_001394893.1:p.His1578Asn missense NM_001407965.1:c.4687C>A NP_001394894.1:p.His1563Asn missense NM_001407966.1:c.4306C>A NP_001394895.1:p.His1436Asn missense NM_001407967.1:c.4303C>A NP_001394896.1:p.His1435Asn missense NM_001407968.1:c.2590C>A NP_001394897.1:p.His864Asn missense NM_001407969.1:c.2587C>A NP_001394898.1:p.His863Asn missense NM_001407970.1:c.1951C>A NP_001394899.1:p.His651Asn missense NM_001407971.1:c.1951C>A NP_001394900.1:p.His651Asn missense NM_001407972.1:c.1948C>A NP_001394901.1:p.His650Asn missense NM_001407973.1:c.1885C>A NP_001394902.1:p.His629Asn missense NM_001407974.1:c.1885C>A NP_001394903.1:p.His629Asn missense NM_001407975.1:c.1885C>A NP_001394904.1:p.His629Asn missense NM_001407976.1:c.1885C>A NP_001394905.1:p.His629Asn missense NM_001407977.1:c.1885C>A NP_001394906.1:p.His629Asn missense NM_001407978.1:c.1885C>A NP_001394907.1:p.His629Asn missense NM_001407979.1:c.1882C>A NP_001394908.1:p.His628Asn missense NM_001407980.1:c.1882C>A NP_001394909.1:p.His628Asn missense NM_001407981.1:c.1882C>A NP_001394910.1:p.His628Asn missense NM_001407982.1:c.1882C>A NP_001394911.1:p.His628Asn missense NM_001407983.1:c.1882C>A NP_001394912.1:p.His628Asn missense NM_001407984.1:c.1882C>A NP_001394913.1:p.His628Asn missense NM_001407985.1:c.1882C>A NP_001394914.1:p.His628Asn missense NM_001407986.1:c.1882C>A NP_001394915.1:p.His628Asn missense NM_001407990.1:c.1882C>A NP_001394919.1:p.His628Asn missense NM_001407991.1:c.1882C>A NP_001394920.1:p.His628Asn missense NM_001407992.1:c.1882C>A NP_001394921.1:p.His628Asn missense NM_001407993.1:c.1882C>A NP_001394922.1:p.His628Asn missense NM_001408392.1:c.1879C>A NP_001395321.1:p.His627Asn missense NM_001408396.1:c.1879C>A NP_001395325.1:p.His627Asn missense NM_001408397.1:c.1879C>A NP_001395326.1:p.His627Asn missense NM_001408398.1:c.1879C>A NP_001395327.1:p.His627Asn missense NM_001408399.1:c.1879C>A NP_001395328.1:p.His627Asn missense NM_001408400.1:c.1879C>A NP_001395329.1:p.His627Asn missense NM_001408401.1:c.1879C>A NP_001395330.1:p.His627Asn missense NM_001408402.1:c.1879C>A NP_001395331.1:p.His627Asn missense NM_001408403.1:c.1879C>A NP_001395332.1:p.His627Asn missense NM_001408404.1:c.1879C>A NP_001395333.1:p.His627Asn missense NM_001408406.1:c.1876C>A NP_001395335.1:p.His626Asn missense NM_001408407.1:c.1876C>A NP_001395336.1:p.His626Asn missense NM_001408408.1:c.1876C>A NP_001395337.1:p.His626Asn missense NM_001408409.1:c.1873C>A NP_001395338.1:p.His625Asn missense NM_001408410.1:c.1810C>A NP_001395339.1:p.His604Asn missense NM_001408411.1:c.1807C>A NP_001395340.1:p.His603Asn missense NM_001408412.1:c.1804C>A NP_001395341.1:p.His602Asn missense NM_001408413.1:c.1804C>A NP_001395342.1:p.His602Asn missense NM_001408414.1:c.1804C>A NP_001395343.1:p.His602Asn missense NM_001408415.1:c.1804C>A NP_001395344.1:p.His602Asn missense NM_001408416.1:c.1804C>A NP_001395345.1:p.His602Asn missense NM_001408418.1:c.1768C>A NP_001395347.1:p.His590Asn missense NM_001408419.1:c.1768C>A NP_001395348.1:p.His590Asn missense NM_001408420.1:c.1768C>A NP_001395349.1:p.His590Asn missense NM_001408421.1:c.1765C>A NP_001395350.1:p.His589Asn missense NM_001408422.1:c.1765C>A NP_001395351.1:p.His589Asn missense NM_001408423.1:c.1765C>A NP_001395352.1:p.His589Asn missense NM_001408424.1:c.1765C>A NP_001395353.1:p.His589Asn missense NM_001408425.1:c.1762C>A NP_001395354.1:p.His588Asn missense NM_001408426.1:c.1762C>A NP_001395355.1:p.His588Asn missense NM_001408427.1:c.1762C>A NP_001395356.1:p.His588Asn missense NM_001408428.1:c.1762C>A NP_001395357.1:p.His588Asn missense NM_001408429.1:c.1762C>A NP_001395358.1:p.His588Asn missense NM_001408430.1:c.1762C>A NP_001395359.1:p.His588Asn missense NM_001408431.1:c.1762C>A NP_001395360.1:p.His588Asn missense NM_001408432.1:c.1759C>A NP_001395361.1:p.His587Asn missense NM_001408433.1:c.1759C>A NP_001395362.1:p.His587Asn missense NM_001408434.1:c.1759C>A NP_001395363.1:p.His587Asn missense NM_001408435.1:c.1759C>A NP_001395364.1:p.His587Asn missense NM_001408436.1:c.1759C>A NP_001395365.1:p.His587Asn missense NM_001408437.1:c.1759C>A NP_001395366.1:p.His587Asn missense NM_001408438.1:c.1759C>A NP_001395367.1:p.His587Asn missense NM_001408439.1:c.1759C>A NP_001395368.1:p.His587Asn missense NM_001408440.1:c.1759C>A NP_001395369.1:p.His587Asn missense NM_001408441.1:c.1759C>A NP_001395370.1:p.His587Asn missense NM_001408442.1:c.1759C>A NP_001395371.1:p.His587Asn missense NM_001408443.1:c.1759C>A NP_001395372.1:p.His587Asn missense NM_001408444.1:c.1759C>A NP_001395373.1:p.His587Asn missense NM_001408445.1:c.1756C>A NP_001395374.1:p.His586Asn missense NM_001408446.1:c.1756C>A NP_001395375.1:p.His586Asn missense NM_001408447.1:c.1756C>A NP_001395376.1:p.His586Asn missense NM_001408448.1:c.1756C>A NP_001395377.1:p.His586Asn missense NM_001408450.1:c.1756C>A NP_001395379.1:p.His586Asn missense NM_001408451.1:c.1750C>A NP_001395380.1:p.His584Asn missense NM_001408452.1:c.1744C>A NP_001395381.1:p.His582Asn missense NM_001408453.1:c.1744C>A NP_001395382.1:p.His582Asn missense NM_001408454.1:c.1744C>A NP_001395383.1:p.His582Asn missense NM_001408455.1:c.1744C>A NP_001395384.1:p.His582Asn missense NM_001408456.1:c.1744C>A NP_001395385.1:p.His582Asn missense NM_001408457.1:c.1744C>A NP_001395386.1:p.His582Asn missense NM_001408458.1:c.1741C>A NP_001395387.1:p.His581Asn missense NM_001408459.1:c.1741C>A NP_001395388.1:p.His581Asn missense NM_001408460.1:c.1741C>A NP_001395389.1:p.His581Asn missense NM_001408461.1:c.1741C>A NP_001395390.1:p.His581Asn missense NM_001408462.1:c.1741C>A NP_001395391.1:p.His581Asn missense NM_001408463.1:c.1741C>A NP_001395392.1:p.His581Asn missense NM_001408464.1:c.1741C>A NP_001395393.1:p.His581Asn missense NM_001408465.1:c.1741C>A NP_001395394.1:p.His581Asn missense NM_001408466.1:c.1741C>A NP_001395395.1:p.His581Asn missense NM_001408467.1:c.1741C>A NP_001395396.1:p.His581Asn missense NM_001408468.1:c.1738C>A NP_001395397.1:p.His580Asn missense NM_001408469.1:c.1738C>A NP_001395398.1:p.His580Asn missense NM_001408470.1:c.1738C>A NP_001395399.1:p.His580Asn missense NM_001408472.1:c.1882C>A NP_001395401.1:p.His628Asn missense NM_001408473.1:c.1879C>A NP_001395402.1:p.His627Asn missense NM_001408474.1:c.1684C>A NP_001395403.1:p.His562Asn missense NM_001408475.1:c.1681C>A NP_001395404.1:p.His561Asn missense NM_001408476.1:c.1681C>A NP_001395405.1:p.His561Asn missense NM_001408478.1:c.1675C>A NP_001395407.1:p.His559Asn missense NM_001408479.1:c.1675C>A NP_001395408.1:p.His559Asn missense NM_001408480.1:c.1675C>A NP_001395409.1:p.His559Asn missense NM_001408481.1:c.1672C>A NP_001395410.1:p.His558Asn missense NM_001408482.1:c.1672C>A NP_001395411.1:p.His558Asn missense NM_001408483.1:c.1672C>A NP_001395412.1:p.His558Asn missense NM_001408484.1:c.1672C>A NP_001395413.1:p.His558Asn missense NM_001408485.1:c.1672C>A NP_001395414.1:p.His558Asn missense NM_001408489.1:c.1672C>A NP_001395418.1:p.His558Asn missense NM_001408490.1:c.1672C>A NP_001395419.1:p.His558Asn missense NM_001408491.1:c.1672C>A NP_001395420.1:p.His558Asn missense NM_001408492.1:c.1669C>A NP_001395421.1:p.His557Asn missense NM_001408493.1:c.1669C>A NP_001395422.1:p.His557Asn missense NM_001408494.1:c.1645C>A NP_001395423.1:p.His549Asn missense NM_001408495.1:c.1639C>A NP_001395424.1:p.His547Asn missense NM_001408496.1:c.1621C>A NP_001395425.1:p.His541Asn missense NM_001408497.1:c.1621C>A NP_001395426.1:p.His541Asn missense NM_001408498.1:c.1621C>A NP_001395427.1:p.His541Asn missense NM_001408499.1:c.1621C>A NP_001395428.1:p.His541Asn missense NM_001408500.1:c.1621C>A NP_001395429.1:p.His541Asn missense NM_001408501.1:c.1621C>A NP_001395430.1:p.His541Asn missense NM_001408502.1:c.1618C>A NP_001395431.1:p.His540Asn missense NM_001408503.1:c.1618C>A NP_001395432.1:p.His540Asn missense NM_001408504.1:c.1618C>A NP_001395433.1:p.His540Asn missense NM_001408505.1:c.1615C>A NP_001395434.1:p.His539Asn missense NM_001408506.1:c.1558C>A NP_001395435.1:p.His520Asn missense NM_001408507.1:c.1555C>A NP_001395436.1:p.His519Asn missense NM_001408508.1:c.1546C>A NP_001395437.1:p.His516Asn missense NM_001408509.1:c.1543C>A NP_001395438.1:p.His515Asn missense NM_001408510.1:c.1504C>A NP_001395439.1:p.His502Asn missense NM_001408511.1:c.1501C>A NP_001395440.1:p.His501Asn missense NM_001408512.1:c.1381C>A NP_001395441.1:p.His461Asn missense NM_001408513.1:c.1354C>A NP_001395442.1:p.His452Asn missense NM_001408514.1:c.958C>A NP_001395443.1:p.His320Asn missense NM_007297.4:c.5053C>A NP_009228.2:p.His1685Asn missense NM_007298.4:c.1882C>A NP_009229.2:p.His628Asn missense NM_007299.4:c.1882C>A NP_009230.2:p.His628Asn missense NM_007300.4:c.5257C>A NP_009231.2:p.His1753Asn missense NM_007304.2:c.1882C>A NP_009235.2:p.His628Asn missense NR_027676.2:n.5371C>A non-coding transcript variant NC_000017.11:g.43057135G>T NC_000017.10:g.41209152G>T NG_005905.2:g.160849C>A LRG_292:g.160849C>A LRG_292t1:c.5194C>A LRG_292p1:p.His1732Asn - Protein change
- H1753N, H628N, H1685N, H1732N, H1563N, H1603N, H1642N, H1644N, H1660N, H1662N, H1684N, H1688N, H1704N, H1706N, H1727N, H1729N, H1730N, H1731N, H1752N, H320N, H519N, H539N, H547N, H559N, H584N, H586N, H589N, H602N, H625N, H629N, H1436N, H1619N, H1689N, H1705N, H1712N, H1713N, H516N, H541N, H549N, H590N, H626N, H864N, H1605N, H1620N, H1621N, H1643N, H1663N, H1665N, H1690N, H452N, H461N, H501N, H515N, H520N, H540N, H557N, H561N, H580N, H603N, H604N, H1435N, H1578N, H1604N, H1661N, H1664N, H1683N, H1691N, H1728N, H1754N, H502N, H558N, H562N, H581N, H582N, H587N, H588N, H627N, H650N, H651N, H863N
- Other names
- -
- Canonical SPDI
- NC_000017.11:43057134:G:T
-
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.5194C>A, a MISSENSE variant, produced a function score of -0.59, 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
|
- | RCV001076199.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jun 21, 2022 | RCV002557929.3 |
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
(Jun 21, 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: SCV003213267.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1732 of the BRCA1 protein (p.His1732Asn). … (more)
This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1732 of the BRCA1 protein (p.His1732Asn). 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). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 867500). 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). (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: SCV001241907.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.586664005450233
|
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: SCV001241907.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5194C>A, a MISSENSE variant, produced a function score of -0.59, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5194C>A, a MISSENSE variant, produced a function score of -0.59, 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)
|
Comment:
This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1732 of the BRCA1 protein (p.His1732Asn). 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). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 867500). 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).
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 rs2051531560 ...
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.