This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1708 of the BRCA1 protein (p.Ala1708Thr). This variant is present in population databases (rs397507243, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 37639). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5122G>A (p.Ala1708Thr)
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.
(4)
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
4
criteria provided, multiple submitters, no conflicts
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.5122G>A (p.Ala1708Thr)
Variation ID: 37639 Accession: VCV000037639.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43063904 (GRCh38) [ NCBI UCSC ] 17: 41215921 (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 Sep 27, 2014 May 1, 2024 Jan 15, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5122G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1708Thr missense NM_001407571.1:c.4909G>A NP_001394500.1:p.Ala1637Thr missense NM_001407581.1:c.5188G>A NP_001394510.1:p.Ala1730Thr missense NM_001407582.1:c.5188G>A NP_001394511.1:p.Ala1730Thr missense NM_001407583.1:c.5185G>A NP_001394512.1:p.Ala1729Thr missense NM_001407585.1:c.5185G>A NP_001394514.1:p.Ala1729Thr missense NM_001407587.1:c.5185G>A NP_001394516.1:p.Ala1729Thr missense NM_001407590.1:c.5182G>A NP_001394519.1:p.Ala1728Thr missense NM_001407591.1:c.5182G>A NP_001394520.1:p.Ala1728Thr missense NM_001407593.1:c.5122G>A NP_001394522.1:p.Ala1708Thr missense NM_001407594.1:c.5122G>A NP_001394523.1:p.Ala1708Thr missense NM_001407596.1:c.5122G>A NP_001394525.1:p.Ala1708Thr missense NM_001407597.1:c.5122G>A NP_001394526.1:p.Ala1708Thr missense NM_001407598.1:c.5122G>A NP_001394527.1:p.Ala1708Thr missense NM_001407602.1:c.5122G>A NP_001394531.1:p.Ala1708Thr missense NM_001407603.1:c.5122G>A NP_001394532.1:p.Ala1708Thr missense NM_001407605.1:c.5122G>A NP_001394534.1:p.Ala1708Thr missense NM_001407610.1:c.5119G>A NP_001394539.1:p.Ala1707Thr missense NM_001407611.1:c.5119G>A NP_001394540.1:p.Ala1707Thr missense NM_001407612.1:c.5119G>A NP_001394541.1:p.Ala1707Thr missense NM_001407613.1:c.5119G>A NP_001394542.1:p.Ala1707Thr missense NM_001407614.1:c.5119G>A NP_001394543.1:p.Ala1707Thr missense NM_001407615.1:c.5119G>A NP_001394544.1:p.Ala1707Thr missense NM_001407616.1:c.5119G>A NP_001394545.1:p.Ala1707Thr missense NM_001407617.1:c.5119G>A NP_001394546.1:p.Ala1707Thr missense NM_001407618.1:c.5119G>A NP_001394547.1:p.Ala1707Thr missense NM_001407619.1:c.5119G>A NP_001394548.1:p.Ala1707Thr missense NM_001407620.1:c.5119G>A NP_001394549.1:p.Ala1707Thr missense NM_001407621.1:c.5119G>A NP_001394550.1:p.Ala1707Thr missense NM_001407622.1:c.5119G>A NP_001394551.1:p.Ala1707Thr missense NM_001407623.1:c.5119G>A NP_001394552.1:p.Ala1707Thr missense NM_001407624.1:c.5119G>A NP_001394553.1:p.Ala1707Thr missense NM_001407625.1:c.5119G>A NP_001394554.1:p.Ala1707Thr missense NM_001407626.1:c.5119G>A NP_001394555.1:p.Ala1707Thr missense NM_001407627.1:c.5116G>A NP_001394556.1:p.Ala1706Thr missense NM_001407628.1:c.5116G>A NP_001394557.1:p.Ala1706Thr missense NM_001407629.1:c.5116G>A NP_001394558.1:p.Ala1706Thr missense NM_001407630.1:c.5116G>A NP_001394559.1:p.Ala1706Thr missense NM_001407631.1:c.5116G>A NP_001394560.1:p.Ala1706Thr missense NM_001407632.1:c.5116G>A NP_001394561.1:p.Ala1706Thr missense NM_001407633.1:c.5116G>A NP_001394562.1:p.Ala1706Thr missense NM_001407634.1:c.5116G>A NP_001394563.1:p.Ala1706Thr missense NM_001407635.1:c.5116G>A NP_001394564.1:p.Ala1706Thr missense NM_001407636.1:c.5116G>A NP_001394565.1:p.Ala1706Thr missense NM_001407637.1:c.5116G>A NP_001394566.1:p.Ala1706Thr missense NM_001407638.1:c.5116G>A NP_001394567.1:p.Ala1706Thr missense NM_001407639.1:c.5116G>A NP_001394568.1:p.Ala1706Thr missense NM_001407640.1:c.5116G>A NP_001394569.1:p.Ala1706Thr missense NM_001407641.1:c.5116G>A NP_001394570.1:p.Ala1706Thr missense NM_001407642.1:c.5116G>A NP_001394571.1:p.Ala1706Thr missense NM_001407644.1:c.5113G>A NP_001394573.1:p.Ala1705Thr missense NM_001407645.1:c.5113G>A NP_001394574.1:p.Ala1705Thr missense NM_001407646.1:c.5110G>A NP_001394575.1:p.Ala1704Thr missense NM_001407647.1:c.5107G>A NP_001394576.1:p.Ala1703Thr missense NM_001407648.1:c.5065G>A NP_001394577.1:p.Ala1689Thr missense NM_001407649.1:c.5062G>A NP_001394578.1:p.Ala1688Thr missense NM_001407653.1:c.5044G>A NP_001394582.1:p.Ala1682Thr missense NM_001407654.1:c.5044G>A NP_001394583.1:p.Ala1682Thr missense NM_001407655.1:c.5044G>A NP_001394584.1:p.Ala1682Thr missense NM_001407656.1:c.5041G>A NP_001394585.1:p.Ala1681Thr missense NM_001407657.1:c.5041G>A NP_001394586.1:p.Ala1681Thr missense NM_001407658.1:c.5041G>A NP_001394587.1:p.Ala1681Thr missense NM_001407659.1:c.5038G>A NP_001394588.1:p.Ala1680Thr missense NM_001407660.1:c.5038G>A NP_001394589.1:p.Ala1680Thr missense NM_001407661.1:c.5038G>A NP_001394590.1:p.Ala1680Thr missense NM_001407662.1:c.5038G>A NP_001394591.1:p.Ala1680Thr missense NM_001407663.1:c.5038G>A NP_001394592.1:p.Ala1680Thr missense NM_001407664.1:c.4999G>A NP_001394593.1:p.Ala1667Thr missense NM_001407665.1:c.4999G>A NP_001394594.1:p.Ala1667Thr missense NM_001407666.1:c.4999G>A NP_001394595.1:p.Ala1667Thr missense NM_001407667.1:c.4999G>A NP_001394596.1:p.Ala1667Thr missense NM_001407668.1:c.4999G>A NP_001394597.1:p.Ala1667Thr missense NM_001407669.1:c.4999G>A NP_001394598.1:p.Ala1667Thr missense NM_001407670.1:c.4996G>A NP_001394599.1:p.Ala1666Thr missense NM_001407671.1:c.4996G>A NP_001394600.1:p.Ala1666Thr missense NM_001407672.1:c.4996G>A NP_001394601.1:p.Ala1666Thr missense NM_001407673.1:c.4996G>A NP_001394602.1:p.Ala1666Thr missense NM_001407674.1:c.4996G>A NP_001394603.1:p.Ala1666Thr missense NM_001407675.1:c.4996G>A NP_001394604.1:p.Ala1666Thr missense NM_001407676.1:c.4996G>A NP_001394605.1:p.Ala1666Thr missense NM_001407677.1:c.4996G>A NP_001394606.1:p.Ala1666Thr missense NM_001407678.1:c.4996G>A NP_001394607.1:p.Ala1666Thr missense NM_001407679.1:c.4996G>A NP_001394608.1:p.Ala1666Thr missense NM_001407680.1:c.4996G>A NP_001394609.1:p.Ala1666Thr missense NM_001407681.1:c.4993G>A NP_001394610.1:p.Ala1665Thr missense NM_001407682.1:c.4993G>A NP_001394611.1:p.Ala1665Thr missense NM_001407683.1:c.4993G>A NP_001394612.1:p.Ala1665Thr missense NM_001407684.1:c.5122G>A NP_001394613.1:p.Ala1708Thr missense NM_001407685.1:c.4993G>A NP_001394614.1:p.Ala1665Thr missense NM_001407686.1:c.4993G>A NP_001394615.1:p.Ala1665Thr missense NM_001407687.1:c.4993G>A NP_001394616.1:p.Ala1665Thr missense NM_001407688.1:c.4993G>A NP_001394617.1:p.Ala1665Thr missense NM_001407689.1:c.4993G>A NP_001394618.1:p.Ala1665Thr missense NM_001407690.1:c.4990G>A NP_001394619.1:p.Ala1664Thr missense NM_001407691.1:c.4990G>A NP_001394620.1:p.Ala1664Thr missense NM_001407692.1:c.4981G>A NP_001394621.1:p.Ala1661Thr missense NM_001407694.1:c.4981G>A NP_001394623.1:p.Ala1661Thr missense NM_001407695.1:c.4981G>A NP_001394624.1:p.Ala1661Thr missense NM_001407696.1:c.4981G>A NP_001394625.1:p.Ala1661Thr missense NM_001407697.1:c.4981G>A NP_001394626.1:p.Ala1661Thr missense NM_001407698.1:c.4981G>A NP_001394627.1:p.Ala1661Thr missense NM_001407724.1:c.4981G>A NP_001394653.1:p.Ala1661Thr missense NM_001407725.1:c.4981G>A NP_001394654.1:p.Ala1661Thr missense NM_001407726.1:c.4981G>A NP_001394655.1:p.Ala1661Thr missense NM_001407727.1:c.4981G>A NP_001394656.1:p.Ala1661Thr missense NM_001407728.1:c.4981G>A NP_001394657.1:p.Ala1661Thr missense NM_001407729.1:c.4981G>A NP_001394658.1:p.Ala1661Thr missense NM_001407730.1:c.4981G>A NP_001394659.1:p.Ala1661Thr missense NM_001407731.1:c.4981G>A NP_001394660.1:p.Ala1661Thr missense NM_001407732.1:c.4978G>A NP_001394661.1:p.Ala1660Thr missense NM_001407733.1:c.4978G>A NP_001394662.1:p.Ala1660Thr missense NM_001407734.1:c.4978G>A NP_001394663.1:p.Ala1660Thr missense NM_001407735.1:c.4978G>A NP_001394664.1:p.Ala1660Thr missense NM_001407736.1:c.4978G>A NP_001394665.1:p.Ala1660Thr missense NM_001407737.1:c.4978G>A NP_001394666.1:p.Ala1660Thr missense NM_001407738.1:c.4978G>A NP_001394667.1:p.Ala1660Thr missense NM_001407739.1:c.4978G>A NP_001394668.1:p.Ala1660Thr missense NM_001407740.1:c.4978G>A NP_001394669.1:p.Ala1660Thr missense NM_001407741.1:c.4978G>A NP_001394670.1:p.Ala1660Thr missense NM_001407742.1:c.4978G>A NP_001394671.1:p.Ala1660Thr missense NM_001407743.1:c.4978G>A NP_001394672.1:p.Ala1660Thr missense NM_001407744.1:c.4978G>A NP_001394673.1:p.Ala1660Thr missense NM_001407745.1:c.4978G>A NP_001394674.1:p.Ala1660Thr missense NM_001407746.1:c.4978G>A NP_001394675.1:p.Ala1660Thr missense NM_001407747.1:c.4978G>A NP_001394676.1:p.Ala1660Thr missense NM_001407748.1:c.4978G>A NP_001394677.1:p.Ala1660Thr missense NM_001407749.1:c.4978G>A NP_001394678.1:p.Ala1660Thr missense NM_001407750.1:c.4978G>A NP_001394679.1:p.Ala1660Thr missense NM_001407751.1:c.4978G>A NP_001394680.1:p.Ala1660Thr missense NM_001407752.1:c.4978G>A NP_001394681.1:p.Ala1660Thr missense NM_001407838.1:c.4975G>A NP_001394767.1:p.Ala1659Thr missense NM_001407839.1:c.4975G>A NP_001394768.1:p.Ala1659Thr missense NM_001407841.1:c.4975G>A NP_001394770.1:p.Ala1659Thr missense NM_001407842.1:c.4975G>A NP_001394771.1:p.Ala1659Thr missense NM_001407843.1:c.4975G>A NP_001394772.1:p.Ala1659Thr missense NM_001407844.1:c.4975G>A NP_001394773.1:p.Ala1659Thr missense NM_001407845.1:c.4975G>A NP_001394774.1:p.Ala1659Thr missense NM_001407846.1:c.4975G>A NP_001394775.1:p.Ala1659Thr missense NM_001407847.1:c.4975G>A NP_001394776.1:p.Ala1659Thr missense NM_001407848.1:c.4975G>A NP_001394777.1:p.Ala1659Thr missense NM_001407849.1:c.4975G>A NP_001394778.1:p.Ala1659Thr missense NM_001407850.1:c.4975G>A NP_001394779.1:p.Ala1659Thr missense NM_001407851.1:c.4975G>A NP_001394780.1:p.Ala1659Thr missense NM_001407852.1:c.4975G>A NP_001394781.1:p.Ala1659Thr missense NM_001407853.1:c.4975G>A NP_001394782.1:p.Ala1659Thr missense NM_001407854.1:c.5122G>A NP_001394783.1:p.Ala1708Thr missense NM_001407858.1:c.5119G>A NP_001394787.1:p.Ala1707Thr missense NM_001407859.1:c.5119G>A NP_001394788.1:p.Ala1707Thr missense NM_001407860.1:c.5119G>A NP_001394789.1:p.Ala1707Thr missense NM_001407861.1:c.5116G>A NP_001394790.1:p.Ala1706Thr missense NM_001407862.1:c.4921G>A NP_001394791.1:p.Ala1641Thr missense NM_001407874.1:c.4915G>A NP_001394803.1:p.Ala1639Thr missense NM_001407875.1:c.4915G>A NP_001394804.1:p.Ala1639Thr missense NM_001407879.1:c.4912G>A NP_001394808.1:p.Ala1638Thr missense NM_001407881.1:c.4912G>A NP_001394810.1:p.Ala1638Thr missense NM_001407882.1:c.4912G>A NP_001394811.1:p.Ala1638Thr missense NM_001407884.1:c.4912G>A NP_001394813.1:p.Ala1638Thr missense NM_001407885.1:c.4912G>A NP_001394814.1:p.Ala1638Thr missense NM_001407886.1:c.4912G>A NP_001394815.1:p.Ala1638Thr missense NM_001407887.1:c.4912G>A NP_001394816.1:p.Ala1638Thr missense NM_001407889.1:c.4912G>A NP_001394818.1:p.Ala1638Thr missense NM_001407894.1:c.4909G>A NP_001394823.1:p.Ala1637Thr missense NM_001407895.1:c.4909G>A NP_001394824.1:p.Ala1637Thr missense NM_001407896.1:c.4909G>A NP_001394825.1:p.Ala1637Thr missense NM_001407897.1:c.4909G>A NP_001394826.1:p.Ala1637Thr missense NM_001407898.1:c.4909G>A NP_001394827.1:p.Ala1637Thr missense NM_001407899.1:c.4909G>A NP_001394828.1:p.Ala1637Thr missense NM_001407900.1:c.4909G>A NP_001394829.1:p.Ala1637Thr missense NM_001407902.1:c.4909G>A NP_001394831.1:p.Ala1637Thr missense NM_001407904.1:c.4909G>A NP_001394833.1:p.Ala1637Thr missense NM_001407906.1:c.4909G>A NP_001394835.1:p.Ala1637Thr missense NM_001407907.1:c.4909G>A NP_001394836.1:p.Ala1637Thr missense NM_001407908.1:c.4909G>A NP_001394837.1:p.Ala1637Thr missense NM_001407909.1:c.4909G>A NP_001394838.1:p.Ala1637Thr missense NM_001407910.1:c.4909G>A NP_001394839.1:p.Ala1637Thr missense NM_001407915.1:c.4906G>A NP_001394844.1:p.Ala1636Thr missense NM_001407916.1:c.4906G>A NP_001394845.1:p.Ala1636Thr missense NM_001407917.1:c.4906G>A NP_001394846.1:p.Ala1636Thr missense NM_001407918.1:c.4906G>A NP_001394847.1:p.Ala1636Thr missense NM_001407919.1:c.4999G>A NP_001394848.1:p.Ala1667Thr missense NM_001407920.1:c.4858G>A NP_001394849.1:p.Ala1620Thr missense NM_001407921.1:c.4858G>A NP_001394850.1:p.Ala1620Thr missense NM_001407922.1:c.4858G>A NP_001394851.1:p.Ala1620Thr missense NM_001407923.1:c.4858G>A NP_001394852.1:p.Ala1620Thr missense NM_001407924.1:c.4858G>A NP_001394853.1:p.Ala1620Thr missense NM_001407925.1:c.4858G>A NP_001394854.1:p.Ala1620Thr missense NM_001407926.1:c.4858G>A NP_001394855.1:p.Ala1620Thr missense NM_001407927.1:c.4855G>A NP_001394856.1:p.Ala1619Thr missense NM_001407928.1:c.4855G>A NP_001394857.1:p.Ala1619Thr missense NM_001407929.1:c.4855G>A NP_001394858.1:p.Ala1619Thr missense NM_001407930.1:c.4855G>A NP_001394859.1:p.Ala1619Thr missense NM_001407931.1:c.4855G>A NP_001394860.1:p.Ala1619Thr missense NM_001407932.1:c.4855G>A NP_001394861.1:p.Ala1619Thr missense NM_001407933.1:c.4855G>A NP_001394862.1:p.Ala1619Thr missense NM_001407934.1:c.4852G>A NP_001394863.1:p.Ala1618Thr missense NM_001407935.1:c.4852G>A NP_001394864.1:p.Ala1618Thr missense NM_001407936.1:c.4852G>A NP_001394865.1:p.Ala1618Thr missense NM_001407937.1:c.4999G>A NP_001394866.1:p.Ala1667Thr missense NM_001407938.1:c.4999G>A NP_001394867.1:p.Ala1667Thr missense NM_001407939.1:c.4996G>A NP_001394868.1:p.Ala1666Thr missense NM_001407940.1:c.4996G>A NP_001394869.1:p.Ala1666Thr missense NM_001407941.1:c.4993G>A NP_001394870.1:p.Ala1665Thr missense NM_001407942.1:c.4981G>A NP_001394871.1:p.Ala1661Thr missense NM_001407943.1:c.4978G>A NP_001394872.1:p.Ala1660Thr missense NM_001407944.1:c.4978G>A NP_001394873.1:p.Ala1660Thr missense NM_001407945.1:c.4978G>A NP_001394874.1:p.Ala1660Thr missense NM_001407946.1:c.4789G>A NP_001394875.1:p.Ala1597Thr missense NM_001407947.1:c.4789G>A NP_001394876.1:p.Ala1597Thr missense NM_001407948.1:c.4789G>A NP_001394877.1:p.Ala1597Thr missense NM_001407949.1:c.4789G>A NP_001394878.1:p.Ala1597Thr missense NM_001407950.1:c.4786G>A NP_001394879.1:p.Ala1596Thr missense NM_001407951.1:c.4786G>A NP_001394880.1:p.Ala1596Thr missense NM_001407952.1:c.4786G>A NP_001394881.1:p.Ala1596Thr missense NM_001407953.1:c.4786G>A NP_001394882.1:p.Ala1596Thr missense NM_001407954.1:c.4786G>A NP_001394883.1:p.Ala1596Thr missense NM_001407955.1:c.4786G>A NP_001394884.1:p.Ala1596Thr missense NM_001407956.1:c.4783G>A NP_001394885.1:p.Ala1595Thr missense NM_001407957.1:c.4783G>A NP_001394886.1:p.Ala1595Thr missense NM_001407958.1:c.4783G>A NP_001394887.1:p.Ala1595Thr missense NM_001407959.1:c.4741G>A NP_001394888.1:p.Ala1581Thr missense NM_001407960.1:c.4738G>A NP_001394889.1:p.Ala1580Thr missense NM_001407962.1:c.4738G>A NP_001394891.1:p.Ala1580Thr missense NM_001407963.1:c.4735G>A NP_001394892.1:p.Ala1579Thr missense NM_001407964.1:c.4660G>A NP_001394893.1:p.Ala1554Thr missense NM_001407965.1:c.4615G>A NP_001394894.1:p.Ala1539Thr missense NM_001407966.1:c.4234G>A NP_001394895.1:p.Ala1412Thr missense NM_001407967.1:c.4231G>A NP_001394896.1:p.Ala1411Thr missense NM_001407968.1:c.2518G>A NP_001394897.1:p.Ala840Thr missense NM_001407969.1:c.2515G>A NP_001394898.1:p.Ala839Thr missense NM_001407970.1:c.1879G>A NP_001394899.1:p.Ala627Thr missense NM_001407971.1:c.1879G>A NP_001394900.1:p.Ala627Thr missense NM_001407972.1:c.1876G>A NP_001394901.1:p.Ala626Thr missense NM_001407973.1:c.1813G>A NP_001394902.1:p.Ala605Thr missense NM_001407974.1:c.1813G>A NP_001394903.1:p.Ala605Thr missense NM_001407975.1:c.1813G>A NP_001394904.1:p.Ala605Thr missense NM_001407976.1:c.1813G>A NP_001394905.1:p.Ala605Thr missense NM_001407977.1:c.1813G>A NP_001394906.1:p.Ala605Thr missense NM_001407978.1:c.1813G>A NP_001394907.1:p.Ala605Thr missense NM_001407979.1:c.1810G>A NP_001394908.1:p.Ala604Thr missense NM_001407980.1:c.1810G>A NP_001394909.1:p.Ala604Thr missense NM_001407981.1:c.1810G>A NP_001394910.1:p.Ala604Thr missense NM_001407982.1:c.1810G>A NP_001394911.1:p.Ala604Thr missense NM_001407983.1:c.1810G>A NP_001394912.1:p.Ala604Thr missense NM_001407984.1:c.1810G>A NP_001394913.1:p.Ala604Thr missense NM_001407985.1:c.1810G>A NP_001394914.1:p.Ala604Thr missense NM_001407986.1:c.1810G>A NP_001394915.1:p.Ala604Thr missense NM_001407990.1:c.1810G>A NP_001394919.1:p.Ala604Thr missense NM_001407991.1:c.1810G>A NP_001394920.1:p.Ala604Thr missense NM_001407992.1:c.1810G>A NP_001394921.1:p.Ala604Thr missense NM_001407993.1:c.1810G>A NP_001394922.1:p.Ala604Thr missense NM_001408392.1:c.1807G>A NP_001395321.1:p.Ala603Thr missense NM_001408396.1:c.1807G>A NP_001395325.1:p.Ala603Thr missense NM_001408397.1:c.1807G>A NP_001395326.1:p.Ala603Thr missense NM_001408398.1:c.1807G>A NP_001395327.1:p.Ala603Thr missense NM_001408399.1:c.1807G>A NP_001395328.1:p.Ala603Thr missense NM_001408400.1:c.1807G>A NP_001395329.1:p.Ala603Thr missense NM_001408401.1:c.1807G>A NP_001395330.1:p.Ala603Thr missense NM_001408402.1:c.1807G>A NP_001395331.1:p.Ala603Thr missense NM_001408403.1:c.1807G>A NP_001395332.1:p.Ala603Thr missense NM_001408404.1:c.1807G>A NP_001395333.1:p.Ala603Thr missense NM_001408406.1:c.1804G>A NP_001395335.1:p.Ala602Thr missense NM_001408407.1:c.1804G>A NP_001395336.1:p.Ala602Thr missense NM_001408408.1:c.1804G>A NP_001395337.1:p.Ala602Thr missense NM_001408409.1:c.1801G>A NP_001395338.1:p.Ala601Thr missense NM_001408410.1:c.1738G>A NP_001395339.1:p.Ala580Thr missense NM_001408411.1:c.1735G>A NP_001395340.1:p.Ala579Thr missense NM_001408412.1:c.1732G>A NP_001395341.1:p.Ala578Thr missense NM_001408413.1:c.1732G>A NP_001395342.1:p.Ala578Thr missense NM_001408414.1:c.1732G>A NP_001395343.1:p.Ala578Thr missense NM_001408415.1:c.1732G>A NP_001395344.1:p.Ala578Thr missense NM_001408416.1:c.1732G>A NP_001395345.1:p.Ala578Thr missense NM_001408418.1:c.1696G>A NP_001395347.1:p.Ala566Thr missense NM_001408419.1:c.1696G>A NP_001395348.1:p.Ala566Thr missense NM_001408420.1:c.1696G>A NP_001395349.1:p.Ala566Thr missense NM_001408421.1:c.1693G>A NP_001395350.1:p.Ala565Thr missense NM_001408422.1:c.1693G>A NP_001395351.1:p.Ala565Thr missense NM_001408423.1:c.1693G>A NP_001395352.1:p.Ala565Thr missense NM_001408424.1:c.1693G>A NP_001395353.1:p.Ala565Thr missense NM_001408425.1:c.1690G>A NP_001395354.1:p.Ala564Thr missense NM_001408426.1:c.1690G>A NP_001395355.1:p.Ala564Thr missense NM_001408427.1:c.1690G>A NP_001395356.1:p.Ala564Thr missense NM_001408428.1:c.1690G>A NP_001395357.1:p.Ala564Thr missense NM_001408429.1:c.1690G>A NP_001395358.1:p.Ala564Thr missense NM_001408430.1:c.1690G>A NP_001395359.1:p.Ala564Thr missense NM_001408431.1:c.1690G>A NP_001395360.1:p.Ala564Thr missense NM_001408432.1:c.1687G>A NP_001395361.1:p.Ala563Thr missense NM_001408433.1:c.1687G>A NP_001395362.1:p.Ala563Thr missense NM_001408434.1:c.1687G>A NP_001395363.1:p.Ala563Thr missense NM_001408435.1:c.1687G>A NP_001395364.1:p.Ala563Thr missense NM_001408436.1:c.1687G>A NP_001395365.1:p.Ala563Thr missense NM_001408437.1:c.1687G>A NP_001395366.1:p.Ala563Thr missense NM_001408438.1:c.1687G>A NP_001395367.1:p.Ala563Thr missense NM_001408439.1:c.1687G>A NP_001395368.1:p.Ala563Thr missense NM_001408440.1:c.1687G>A NP_001395369.1:p.Ala563Thr missense NM_001408441.1:c.1687G>A NP_001395370.1:p.Ala563Thr missense NM_001408442.1:c.1687G>A NP_001395371.1:p.Ala563Thr missense NM_001408443.1:c.1687G>A NP_001395372.1:p.Ala563Thr missense NM_001408444.1:c.1687G>A NP_001395373.1:p.Ala563Thr missense NM_001408445.1:c.1684G>A NP_001395374.1:p.Ala562Thr missense NM_001408446.1:c.1684G>A NP_001395375.1:p.Ala562Thr missense NM_001408447.1:c.1684G>A NP_001395376.1:p.Ala562Thr missense NM_001408448.1:c.1684G>A NP_001395377.1:p.Ala562Thr missense NM_001408450.1:c.1684G>A NP_001395379.1:p.Ala562Thr missense NM_001408451.1:c.1678G>A NP_001395380.1:p.Ala560Thr missense NM_001408452.1:c.1672G>A NP_001395381.1:p.Ala558Thr missense NM_001408453.1:c.1672G>A NP_001395382.1:p.Ala558Thr missense NM_001408454.1:c.1672G>A NP_001395383.1:p.Ala558Thr missense NM_001408455.1:c.1672G>A NP_001395384.1:p.Ala558Thr missense NM_001408456.1:c.1672G>A NP_001395385.1:p.Ala558Thr missense NM_001408457.1:c.1672G>A NP_001395386.1:p.Ala558Thr missense NM_001408458.1:c.1669G>A NP_001395387.1:p.Ala557Thr missense NM_001408459.1:c.1669G>A NP_001395388.1:p.Ala557Thr missense NM_001408460.1:c.1669G>A NP_001395389.1:p.Ala557Thr missense NM_001408461.1:c.1669G>A NP_001395390.1:p.Ala557Thr missense NM_001408462.1:c.1669G>A NP_001395391.1:p.Ala557Thr missense NM_001408463.1:c.1669G>A NP_001395392.1:p.Ala557Thr missense NM_001408464.1:c.1669G>A NP_001395393.1:p.Ala557Thr missense NM_001408465.1:c.1669G>A NP_001395394.1:p.Ala557Thr missense NM_001408466.1:c.1669G>A NP_001395395.1:p.Ala557Thr missense NM_001408467.1:c.1669G>A NP_001395396.1:p.Ala557Thr missense NM_001408468.1:c.1666G>A NP_001395397.1:p.Ala556Thr missense NM_001408469.1:c.1666G>A NP_001395398.1:p.Ala556Thr missense NM_001408470.1:c.1666G>A NP_001395399.1:p.Ala556Thr missense NM_001408472.1:c.1810G>A NP_001395401.1:p.Ala604Thr missense NM_001408473.1:c.1807G>A NP_001395402.1:p.Ala603Thr missense NM_001408474.1:c.1612G>A NP_001395403.1:p.Ala538Thr missense NM_001408475.1:c.1609G>A NP_001395404.1:p.Ala537Thr missense NM_001408476.1:c.1609G>A NP_001395405.1:p.Ala537Thr missense NM_001408478.1:c.1603G>A NP_001395407.1:p.Ala535Thr missense NM_001408479.1:c.1603G>A NP_001395408.1:p.Ala535Thr missense NM_001408480.1:c.1603G>A NP_001395409.1:p.Ala535Thr missense NM_001408481.1:c.1600G>A NP_001395410.1:p.Ala534Thr missense NM_001408482.1:c.1600G>A NP_001395411.1:p.Ala534Thr missense NM_001408483.1:c.1600G>A NP_001395412.1:p.Ala534Thr missense NM_001408484.1:c.1600G>A NP_001395413.1:p.Ala534Thr missense NM_001408485.1:c.1600G>A NP_001395414.1:p.Ala534Thr missense NM_001408489.1:c.1600G>A NP_001395418.1:p.Ala534Thr missense NM_001408490.1:c.1600G>A NP_001395419.1:p.Ala534Thr missense NM_001408491.1:c.1600G>A NP_001395420.1:p.Ala534Thr missense NM_001408492.1:c.1597G>A NP_001395421.1:p.Ala533Thr missense NM_001408493.1:c.1597G>A NP_001395422.1:p.Ala533Thr missense NM_001408494.1:c.1573G>A NP_001395423.1:p.Ala525Thr missense NM_001408495.1:c.1567G>A NP_001395424.1:p.Ala523Thr missense NM_001408496.1:c.1549G>A NP_001395425.1:p.Ala517Thr missense NM_001408497.1:c.1549G>A NP_001395426.1:p.Ala517Thr missense NM_001408498.1:c.1549G>A NP_001395427.1:p.Ala517Thr missense NM_001408499.1:c.1549G>A NP_001395428.1:p.Ala517Thr missense NM_001408500.1:c.1549G>A NP_001395429.1:p.Ala517Thr missense NM_001408501.1:c.1549G>A NP_001395430.1:p.Ala517Thr missense NM_001408502.1:c.1546G>A NP_001395431.1:p.Ala516Thr missense NM_001408503.1:c.1546G>A NP_001395432.1:p.Ala516Thr missense NM_001408504.1:c.1546G>A NP_001395433.1:p.Ala516Thr missense NM_001408505.1:c.1543G>A NP_001395434.1:p.Ala515Thr missense NM_001408506.1:c.1486G>A NP_001395435.1:p.Ala496Thr missense NM_001408507.1:c.1483G>A NP_001395436.1:p.Ala495Thr missense NM_001408508.1:c.1474G>A NP_001395437.1:p.Ala492Thr missense NM_001408509.1:c.1471G>A NP_001395438.1:p.Ala491Thr missense NM_001408510.1:c.1432G>A NP_001395439.1:p.Ala478Thr missense NM_001408511.1:c.1429G>A NP_001395440.1:p.Ala477Thr missense NM_001408512.1:c.1309G>A NP_001395441.1:p.Ala437Thr missense NM_001408513.1:c.1282G>A NP_001395442.1:p.Ala428Thr missense NM_001408514.1:c.886G>A NP_001395443.1:p.Ala296Thr missense NM_007297.4:c.4981G>A NP_009228.2:p.Ala1661Thr missense NM_007298.4:c.1810G>A NP_009229.2:p.Ala604Thr missense NM_007299.4:c.1810G>A NP_009230.2:p.Ala604Thr missense NM_007300.4:c.5185G>A NP_009231.2:p.Ala1729Thr missense NM_007304.2:c.1810G>A NP_009235.2:p.Ala604Thr missense NR_027676.2:n.5299G>A non-coding transcript variant NC_000017.11:g.43063904C>T NC_000017.10:g.41215921C>T NG_005905.2:g.154080G>A LRG_292:g.154080G>A LRG_292t1:c.5122G>A LRG_292p1:p.Ala1708Thr - Protein change
- A1708T, A1661T, A1729T, A604T, A1539T, A1619T, A1637T, A1639T, A1680T, A1688T, A1705T, A296T, A515T, A516T, A534T, A535T, A564T, A601T, A627T, A1411T, A1412T, A1618T, A1620T, A1666T, A1681T, A1689T, A1704T, A1707T, A1728T, A437T, A478T, A496T, A538T, A560T, A562T, A563T, A603T, A1554T, A1580T, A1597T, A1636T, A1659T, A1660T, A1665T, A1703T, A477T, A491T, A492T, A523T, A525T, A556T, A565T, A579T, A602T, A605T, A839T, A840T, A1579T, A1581T, A1595T, A1596T, A1638T, A1641T, A1664T, A1667T, A1682T, A1730T, A428T, A495T, A517T, A533T, A537T, A557T, A558T, A566T, A578T, A580T, A626T
- Other names
-
A1706T
5241G>A
- Canonical SPDI
- NC_000017.11:43063903:C:T
-
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.5122G>A, a MISSENSE variant, produced a function score of -1.36, 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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
- 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 (2) |
no assertion criteria provided
|
Jan 31, 2012 | RCV000031220.7 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 15, 2024 | RCV000198404.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 10, 2022 | RCV000223569.6 |
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
(Jan 15, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000254994.5
First in ClinVar: Oct 11, 2015 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1708 of the BRCA1 protein (p.Ala1708Thr). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1708 of the BRCA1 protein (p.Ala1708Thr). This variant is present in population databases (rs397507243, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 37639). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(Nov 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000275547.8
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The p.A1708T variant (also known as c.5122G>A), located in coding exon 16 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.A1708T variant (also known as c.5122G>A), located in coding exon 16 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5122. The alanine at codon 1708 is replaced by threonine, an amino acid with similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jan 31, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053820.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
|
|
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: SCV001237648.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-1.35945402070986
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Comment:
Comment:
The p.A1708T variant (also known as c.5122G>A), located in coding exon 16 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5122. The alanine at codon 1708 is replaced by threonine, an amino acid with similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Germline Functional Evidence
| Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237648.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5122G>A, a MISSENSE variant, produced a function score of -1.36, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5122G>A, a MISSENSE variant, produced a function score of -1.36, 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)
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Comment:
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1708 of the BRCA1 protein (p.Ala1708Thr). This variant is present in population databases (rs397507243, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 37639). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The p.A1708T variant (also known as c.5122G>A), located in coding exon 16 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5122. The alanine at codon 1708 is replaced by threonine, an amino acid with similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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 rs397507243 ...
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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.