This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5242G>A (p.Gly1748Ser)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)
Uncertain significance(1); Likely benign(1)
4
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5242G>A (p.Gly1748Ser)
Variation ID: 55475 Accession: VCV000055475.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43057087 (GRCh38) [ NCBI UCSC ] 17: 41209104 (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 Jan 25, 2018 May 1, 2024 Jan 7, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5242G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gly1748Ser missense NM_001407571.1:c.5029G>A NP_001394500.1:p.Gly1677Ser missense NM_001407581.1:c.5308G>A NP_001394510.1:p.Gly1770Ser missense NM_001407582.1:c.5308G>A NP_001394511.1:p.Gly1770Ser missense NM_001407583.1:c.5305G>A NP_001394512.1:p.Gly1769Ser missense NM_001407585.1:c.5305G>A NP_001394514.1:p.Gly1769Ser missense NM_001407587.1:c.5305G>A NP_001394516.1:p.Gly1769Ser missense NM_001407590.1:c.5302G>A NP_001394519.1:p.Gly1768Ser missense NM_001407591.1:c.5302G>A NP_001394520.1:p.Gly1768Ser missense NM_001407593.1:c.5242G>A NP_001394522.1:p.Gly1748Ser missense NM_001407594.1:c.5242G>A NP_001394523.1:p.Gly1748Ser missense NM_001407596.1:c.5242G>A NP_001394525.1:p.Gly1748Ser missense NM_001407597.1:c.5242G>A NP_001394526.1:p.Gly1748Ser missense NM_001407598.1:c.5242G>A NP_001394527.1:p.Gly1748Ser missense NM_001407602.1:c.5242G>A NP_001394531.1:p.Gly1748Ser missense NM_001407603.1:c.5242G>A NP_001394532.1:p.Gly1748Ser missense NM_001407605.1:c.5242G>A NP_001394534.1:p.Gly1748Ser missense NM_001407610.1:c.5239G>A NP_001394539.1:p.Gly1747Ser missense NM_001407611.1:c.5239G>A NP_001394540.1:p.Gly1747Ser missense NM_001407612.1:c.5239G>A NP_001394541.1:p.Gly1747Ser missense NM_001407613.1:c.5239G>A NP_001394542.1:p.Gly1747Ser missense NM_001407614.1:c.5239G>A NP_001394543.1:p.Gly1747Ser missense NM_001407615.1:c.5239G>A NP_001394544.1:p.Gly1747Ser missense NM_001407616.1:c.5239G>A NP_001394545.1:p.Gly1747Ser missense NM_001407617.1:c.5239G>A NP_001394546.1:p.Gly1747Ser missense NM_001407618.1:c.5239G>A NP_001394547.1:p.Gly1747Ser missense NM_001407619.1:c.5239G>A NP_001394548.1:p.Gly1747Ser missense NM_001407620.1:c.5239G>A NP_001394549.1:p.Gly1747Ser missense NM_001407621.1:c.5239G>A NP_001394550.1:p.Gly1747Ser missense NM_001407622.1:c.5239G>A NP_001394551.1:p.Gly1747Ser missense NM_001407623.1:c.5239G>A NP_001394552.1:p.Gly1747Ser missense NM_001407624.1:c.5239G>A NP_001394553.1:p.Gly1747Ser missense NM_001407625.1:c.5239G>A NP_001394554.1:p.Gly1747Ser missense NM_001407626.1:c.5239G>A NP_001394555.1:p.Gly1747Ser missense NM_001407627.1:c.5236G>A NP_001394556.1:p.Gly1746Ser missense NM_001407628.1:c.5236G>A NP_001394557.1:p.Gly1746Ser missense NM_001407629.1:c.5236G>A NP_001394558.1:p.Gly1746Ser missense NM_001407630.1:c.5236G>A NP_001394559.1:p.Gly1746Ser missense NM_001407631.1:c.5236G>A NP_001394560.1:p.Gly1746Ser missense NM_001407632.1:c.5236G>A NP_001394561.1:p.Gly1746Ser missense NM_001407633.1:c.5236G>A NP_001394562.1:p.Gly1746Ser missense NM_001407634.1:c.5236G>A NP_001394563.1:p.Gly1746Ser missense NM_001407635.1:c.5236G>A NP_001394564.1:p.Gly1746Ser missense NM_001407636.1:c.5236G>A NP_001394565.1:p.Gly1746Ser missense NM_001407637.1:c.5236G>A NP_001394566.1:p.Gly1746Ser missense NM_001407638.1:c.5236G>A NP_001394567.1:p.Gly1746Ser missense NM_001407639.1:c.5236G>A NP_001394568.1:p.Gly1746Ser missense NM_001407640.1:c.5236G>A NP_001394569.1:p.Gly1746Ser missense NM_001407641.1:c.5236G>A NP_001394570.1:p.Gly1746Ser missense NM_001407642.1:c.5236G>A NP_001394571.1:p.Gly1746Ser missense NM_001407644.1:c.5233G>A NP_001394573.1:p.Gly1745Ser missense NM_001407645.1:c.5233G>A NP_001394574.1:p.Gly1745Ser missense NM_001407646.1:c.5230G>A NP_001394575.1:p.Gly1744Ser missense NM_001407647.1:c.5227G>A NP_001394576.1:p.Gly1743Ser missense NM_001407648.1:c.5185G>A NP_001394577.1:p.Gly1729Ser missense NM_001407649.1:c.5182G>A NP_001394578.1:p.Gly1728Ser missense NM_001407652.1:c.5164G>A NP_001394581.1:p.Gly1722Ser missense NM_001407653.1:c.5164G>A NP_001394582.1:p.Gly1722Ser missense NM_001407654.1:c.5164G>A NP_001394583.1:p.Gly1722Ser missense NM_001407655.1:c.5164G>A NP_001394584.1:p.Gly1722Ser missense NM_001407656.1:c.5161G>A NP_001394585.1:p.Gly1721Ser missense NM_001407657.1:c.5161G>A NP_001394586.1:p.Gly1721Ser missense NM_001407658.1:c.5161G>A NP_001394587.1:p.Gly1721Ser missense NM_001407659.1:c.5158G>A NP_001394588.1:p.Gly1720Ser missense NM_001407660.1:c.5158G>A NP_001394589.1:p.Gly1720Ser missense NM_001407661.1:c.5158G>A NP_001394590.1:p.Gly1720Ser missense NM_001407662.1:c.5158G>A NP_001394591.1:p.Gly1720Ser missense NM_001407663.1:c.5158G>A NP_001394592.1:p.Gly1720Ser missense NM_001407664.1:c.5119G>A NP_001394593.1:p.Gly1707Ser missense NM_001407665.1:c.5119G>A NP_001394594.1:p.Gly1707Ser missense NM_001407666.1:c.5119G>A NP_001394595.1:p.Gly1707Ser missense NM_001407667.1:c.5119G>A NP_001394596.1:p.Gly1707Ser missense NM_001407668.1:c.5119G>A NP_001394597.1:p.Gly1707Ser missense NM_001407669.1:c.5119G>A NP_001394598.1:p.Gly1707Ser missense NM_001407670.1:c.5116G>A NP_001394599.1:p.Gly1706Ser missense NM_001407671.1:c.5116G>A NP_001394600.1:p.Gly1706Ser missense NM_001407672.1:c.5116G>A NP_001394601.1:p.Gly1706Ser missense NM_001407673.1:c.5116G>A NP_001394602.1:p.Gly1706Ser missense NM_001407674.1:c.5116G>A NP_001394603.1:p.Gly1706Ser missense NM_001407675.1:c.5116G>A NP_001394604.1:p.Gly1706Ser missense NM_001407676.1:c.5116G>A NP_001394605.1:p.Gly1706Ser missense NM_001407677.1:c.5116G>A NP_001394606.1:p.Gly1706Ser missense NM_001407678.1:c.5116G>A NP_001394607.1:p.Gly1706Ser missense NM_001407679.1:c.5116G>A NP_001394608.1:p.Gly1706Ser missense NM_001407680.1:c.5116G>A NP_001394609.1:p.Gly1706Ser missense NM_001407681.1:c.5113G>A NP_001394610.1:p.Gly1705Ser missense NM_001407682.1:c.5113G>A NP_001394611.1:p.Gly1705Ser missense NM_001407683.1:c.5113G>A NP_001394612.1:p.Gly1705Ser missense NM_001407684.1:c.5242G>A NP_001394613.1:p.Gly1748Ser missense NM_001407685.1:c.5113G>A NP_001394614.1:p.Gly1705Ser missense NM_001407686.1:c.5113G>A NP_001394615.1:p.Gly1705Ser missense NM_001407687.1:c.5113G>A NP_001394616.1:p.Gly1705Ser missense NM_001407688.1:c.5113G>A NP_001394617.1:p.Gly1705Ser missense NM_001407689.1:c.5113G>A NP_001394618.1:p.Gly1705Ser missense NM_001407690.1:c.5110G>A NP_001394619.1:p.Gly1704Ser missense NM_001407691.1:c.5110G>A NP_001394620.1:p.Gly1704Ser missense NM_001407692.1:c.5101G>A NP_001394621.1:p.Gly1701Ser missense NM_001407694.1:c.5101G>A NP_001394623.1:p.Gly1701Ser missense NM_001407695.1:c.5101G>A NP_001394624.1:p.Gly1701Ser missense NM_001407696.1:c.5101G>A NP_001394625.1:p.Gly1701Ser missense NM_001407697.1:c.5101G>A NP_001394626.1:p.Gly1701Ser missense NM_001407698.1:c.5101G>A NP_001394627.1:p.Gly1701Ser missense NM_001407724.1:c.5101G>A NP_001394653.1:p.Gly1701Ser missense NM_001407725.1:c.5101G>A NP_001394654.1:p.Gly1701Ser missense NM_001407726.1:c.5101G>A NP_001394655.1:p.Gly1701Ser missense NM_001407727.1:c.5101G>A NP_001394656.1:p.Gly1701Ser missense NM_001407728.1:c.5101G>A NP_001394657.1:p.Gly1701Ser missense NM_001407729.1:c.5101G>A NP_001394658.1:p.Gly1701Ser missense NM_001407730.1:c.5101G>A NP_001394659.1:p.Gly1701Ser missense NM_001407731.1:c.5101G>A NP_001394660.1:p.Gly1701Ser missense NM_001407732.1:c.5098G>A NP_001394661.1:p.Gly1700Ser missense NM_001407733.1:c.5098G>A NP_001394662.1:p.Gly1700Ser missense NM_001407734.1:c.5098G>A NP_001394663.1:p.Gly1700Ser missense NM_001407735.1:c.5098G>A NP_001394664.1:p.Gly1700Ser missense NM_001407736.1:c.5098G>A NP_001394665.1:p.Gly1700Ser missense NM_001407737.1:c.5098G>A NP_001394666.1:p.Gly1700Ser missense NM_001407738.1:c.5098G>A NP_001394667.1:p.Gly1700Ser missense NM_001407739.1:c.5098G>A NP_001394668.1:p.Gly1700Ser missense NM_001407740.1:c.5098G>A NP_001394669.1:p.Gly1700Ser missense NM_001407741.1:c.5098G>A NP_001394670.1:p.Gly1700Ser missense NM_001407742.1:c.5098G>A NP_001394671.1:p.Gly1700Ser missense NM_001407743.1:c.5098G>A NP_001394672.1:p.Gly1700Ser missense NM_001407744.1:c.5098G>A NP_001394673.1:p.Gly1700Ser missense NM_001407745.1:c.5098G>A NP_001394674.1:p.Gly1700Ser missense NM_001407746.1:c.5098G>A NP_001394675.1:p.Gly1700Ser missense NM_001407747.1:c.5098G>A NP_001394676.1:p.Gly1700Ser missense NM_001407748.1:c.5098G>A NP_001394677.1:p.Gly1700Ser missense NM_001407749.1:c.5098G>A NP_001394678.1:p.Gly1700Ser missense NM_001407750.1:c.5098G>A NP_001394679.1:p.Gly1700Ser missense NM_001407751.1:c.5098G>A NP_001394680.1:p.Gly1700Ser missense NM_001407752.1:c.5098G>A NP_001394681.1:p.Gly1700Ser missense NM_001407838.1:c.5095G>A NP_001394767.1:p.Gly1699Ser missense NM_001407839.1:c.5095G>A NP_001394768.1:p.Gly1699Ser missense NM_001407841.1:c.5095G>A NP_001394770.1:p.Gly1699Ser missense NM_001407842.1:c.5095G>A NP_001394771.1:p.Gly1699Ser missense NM_001407843.1:c.5095G>A NP_001394772.1:p.Gly1699Ser missense NM_001407844.1:c.5095G>A NP_001394773.1:p.Gly1699Ser missense NM_001407845.1:c.5095G>A NP_001394774.1:p.Gly1699Ser missense NM_001407846.1:c.5095G>A NP_001394775.1:p.Gly1699Ser missense NM_001407847.1:c.5095G>A NP_001394776.1:p.Gly1699Ser missense NM_001407848.1:c.5095G>A NP_001394777.1:p.Gly1699Ser missense NM_001407849.1:c.5095G>A NP_001394778.1:p.Gly1699Ser missense NM_001407850.1:c.5095G>A NP_001394779.1:p.Gly1699Ser missense NM_001407851.1:c.5095G>A NP_001394780.1:p.Gly1699Ser missense NM_001407852.1:c.5095G>A NP_001394781.1:p.Gly1699Ser missense NM_001407853.1:c.5095G>A NP_001394782.1:p.Gly1699Ser missense NM_001407854.1:c.5242G>A NP_001394783.1:p.Gly1748Ser missense NM_001407858.1:c.5239G>A NP_001394787.1:p.Gly1747Ser missense NM_001407859.1:c.5239G>A NP_001394788.1:p.Gly1747Ser missense NM_001407860.1:c.5239G>A NP_001394789.1:p.Gly1747Ser missense NM_001407861.1:c.5236G>A NP_001394790.1:p.Gly1746Ser missense NM_001407862.1:c.5041G>A NP_001394791.1:p.Gly1681Ser missense NM_001407863.1:c.5038G>A NP_001394792.1:p.Gly1680Ser missense NM_001407874.1:c.5035G>A NP_001394803.1:p.Gly1679Ser missense NM_001407875.1:c.5035G>A NP_001394804.1:p.Gly1679Ser missense NM_001407879.1:c.5032G>A NP_001394808.1:p.Gly1678Ser missense NM_001407881.1:c.5032G>A NP_001394810.1:p.Gly1678Ser missense NM_001407882.1:c.5032G>A NP_001394811.1:p.Gly1678Ser missense NM_001407884.1:c.5032G>A NP_001394813.1:p.Gly1678Ser missense NM_001407885.1:c.5032G>A NP_001394814.1:p.Gly1678Ser missense NM_001407886.1:c.5032G>A NP_001394815.1:p.Gly1678Ser missense NM_001407887.1:c.5032G>A NP_001394816.1:p.Gly1678Ser missense NM_001407889.1:c.5032G>A NP_001394818.1:p.Gly1678Ser missense NM_001407894.1:c.5029G>A NP_001394823.1:p.Gly1677Ser missense NM_001407895.1:c.5029G>A NP_001394824.1:p.Gly1677Ser missense NM_001407896.1:c.5029G>A NP_001394825.1:p.Gly1677Ser missense NM_001407897.1:c.5029G>A NP_001394826.1:p.Gly1677Ser missense NM_001407898.1:c.5029G>A NP_001394827.1:p.Gly1677Ser missense NM_001407899.1:c.5029G>A NP_001394828.1:p.Gly1677Ser missense NM_001407900.1:c.5029G>A NP_001394829.1:p.Gly1677Ser missense NM_001407902.1:c.5029G>A NP_001394831.1:p.Gly1677Ser missense NM_001407904.1:c.5029G>A NP_001394833.1:p.Gly1677Ser missense NM_001407906.1:c.5029G>A NP_001394835.1:p.Gly1677Ser missense NM_001407907.1:c.5029G>A NP_001394836.1:p.Gly1677Ser missense NM_001407908.1:c.5029G>A NP_001394837.1:p.Gly1677Ser missense NM_001407909.1:c.5029G>A NP_001394838.1:p.Gly1677Ser missense NM_001407910.1:c.5029G>A NP_001394839.1:p.Gly1677Ser missense NM_001407915.1:c.5026G>A NP_001394844.1:p.Gly1676Ser missense NM_001407916.1:c.5026G>A NP_001394845.1:p.Gly1676Ser missense NM_001407917.1:c.5026G>A NP_001394846.1:p.Gly1676Ser missense NM_001407918.1:c.5026G>A NP_001394847.1:p.Gly1676Ser missense NM_001407919.1:c.5119G>A NP_001394848.1:p.Gly1707Ser missense NM_001407920.1:c.4978G>A NP_001394849.1:p.Gly1660Ser missense NM_001407921.1:c.4978G>A NP_001394850.1:p.Gly1660Ser missense NM_001407922.1:c.4978G>A NP_001394851.1:p.Gly1660Ser missense NM_001407923.1:c.4978G>A NP_001394852.1:p.Gly1660Ser missense NM_001407924.1:c.4978G>A NP_001394853.1:p.Gly1660Ser missense NM_001407925.1:c.4978G>A NP_001394854.1:p.Gly1660Ser missense NM_001407926.1:c.4978G>A NP_001394855.1:p.Gly1660Ser missense NM_001407927.1:c.4975G>A NP_001394856.1:p.Gly1659Ser missense NM_001407928.1:c.4975G>A NP_001394857.1:p.Gly1659Ser missense NM_001407929.1:c.4975G>A NP_001394858.1:p.Gly1659Ser missense NM_001407930.1:c.4975G>A NP_001394859.1:p.Gly1659Ser missense NM_001407931.1:c.4975G>A NP_001394860.1:p.Gly1659Ser missense NM_001407932.1:c.4975G>A NP_001394861.1:p.Gly1659Ser missense NM_001407933.1:c.4975G>A NP_001394862.1:p.Gly1659Ser missense NM_001407934.1:c.4972G>A NP_001394863.1:p.Gly1658Ser missense NM_001407935.1:c.4972G>A NP_001394864.1:p.Gly1658Ser missense NM_001407936.1:c.4972G>A NP_001394865.1:p.Gly1658Ser missense NM_001407937.1:c.5119G>A NP_001394866.1:p.Gly1707Ser missense NM_001407938.1:c.5119G>A NP_001394867.1:p.Gly1707Ser missense NM_001407939.1:c.5116G>A NP_001394868.1:p.Gly1706Ser missense NM_001407940.1:c.5116G>A NP_001394869.1:p.Gly1706Ser missense NM_001407941.1:c.5113G>A NP_001394870.1:p.Gly1705Ser missense NM_001407942.1:c.5101G>A NP_001394871.1:p.Gly1701Ser missense NM_001407943.1:c.5098G>A NP_001394872.1:p.Gly1700Ser missense NM_001407944.1:c.5098G>A NP_001394873.1:p.Gly1700Ser missense NM_001407945.1:c.5098G>A NP_001394874.1:p.Gly1700Ser missense NM_001407946.1:c.4909G>A NP_001394875.1:p.Gly1637Ser missense NM_001407947.1:c.4909G>A NP_001394876.1:p.Gly1637Ser missense NM_001407948.1:c.4909G>A NP_001394877.1:p.Gly1637Ser missense NM_001407949.1:c.4909G>A NP_001394878.1:p.Gly1637Ser missense NM_001407950.1:c.4906G>A NP_001394879.1:p.Gly1636Ser missense NM_001407951.1:c.4906G>A NP_001394880.1:p.Gly1636Ser missense NM_001407952.1:c.4906G>A NP_001394881.1:p.Gly1636Ser missense NM_001407953.1:c.4906G>A NP_001394882.1:p.Gly1636Ser missense NM_001407954.1:c.4906G>A NP_001394883.1:p.Gly1636Ser missense NM_001407955.1:c.4906G>A NP_001394884.1:p.Gly1636Ser missense NM_001407956.1:c.4903G>A NP_001394885.1:p.Gly1635Ser missense NM_001407957.1:c.4903G>A NP_001394886.1:p.Gly1635Ser missense NM_001407958.1:c.4903G>A NP_001394887.1:p.Gly1635Ser missense NM_001407959.1:c.4861G>A NP_001394888.1:p.Gly1621Ser missense NM_001407960.1:c.4858G>A NP_001394889.1:p.Gly1620Ser missense NM_001407962.1:c.4858G>A NP_001394891.1:p.Gly1620Ser missense NM_001407963.1:c.4855G>A NP_001394892.1:p.Gly1619Ser missense NM_001407964.1:c.4780G>A NP_001394893.1:p.Gly1594Ser missense NM_001407965.1:c.4735G>A NP_001394894.1:p.Gly1579Ser missense NM_001407966.1:c.4354G>A NP_001394895.1:p.Gly1452Ser missense NM_001407967.1:c.4351G>A NP_001394896.1:p.Gly1451Ser missense NM_001407968.1:c.2638G>A NP_001394897.1:p.Gly880Ser missense NM_001407969.1:c.2635G>A NP_001394898.1:p.Gly879Ser missense NM_001407970.1:c.1999G>A NP_001394899.1:p.Gly667Ser missense NM_001407971.1:c.1999G>A NP_001394900.1:p.Gly667Ser missense NM_001407972.1:c.1996G>A NP_001394901.1:p.Gly666Ser missense NM_001407973.1:c.1933G>A NP_001394902.1:p.Gly645Ser missense NM_001407974.1:c.1933G>A NP_001394903.1:p.Gly645Ser missense NM_001407975.1:c.1933G>A NP_001394904.1:p.Gly645Ser missense NM_001407976.1:c.1933G>A NP_001394905.1:p.Gly645Ser missense NM_001407977.1:c.1933G>A NP_001394906.1:p.Gly645Ser missense NM_001407978.1:c.1933G>A NP_001394907.1:p.Gly645Ser missense NM_001407979.1:c.1930G>A NP_001394908.1:p.Gly644Ser missense NM_001407980.1:c.1930G>A NP_001394909.1:p.Gly644Ser missense NM_001407981.1:c.1930G>A NP_001394910.1:p.Gly644Ser missense NM_001407982.1:c.1930G>A NP_001394911.1:p.Gly644Ser missense NM_001407983.1:c.1930G>A NP_001394912.1:p.Gly644Ser missense NM_001407984.1:c.1930G>A NP_001394913.1:p.Gly644Ser missense NM_001407985.1:c.1930G>A NP_001394914.1:p.Gly644Ser missense NM_001407986.1:c.1930G>A NP_001394915.1:p.Gly644Ser missense NM_001407990.1:c.1930G>A NP_001394919.1:p.Gly644Ser missense NM_001407991.1:c.1930G>A NP_001394920.1:p.Gly644Ser missense NM_001407992.1:c.1930G>A NP_001394921.1:p.Gly644Ser missense NM_001407993.1:c.1930G>A NP_001394922.1:p.Gly644Ser missense NM_001408392.1:c.1927G>A NP_001395321.1:p.Gly643Ser missense NM_001408396.1:c.1927G>A NP_001395325.1:p.Gly643Ser missense NM_001408397.1:c.1927G>A NP_001395326.1:p.Gly643Ser missense NM_001408398.1:c.1927G>A NP_001395327.1:p.Gly643Ser missense NM_001408399.1:c.1927G>A NP_001395328.1:p.Gly643Ser missense NM_001408400.1:c.1927G>A NP_001395329.1:p.Gly643Ser missense NM_001408401.1:c.1927G>A NP_001395330.1:p.Gly643Ser missense NM_001408402.1:c.1927G>A NP_001395331.1:p.Gly643Ser missense NM_001408403.1:c.1927G>A NP_001395332.1:p.Gly643Ser missense NM_001408404.1:c.1927G>A NP_001395333.1:p.Gly643Ser missense NM_001408406.1:c.1924G>A NP_001395335.1:p.Gly642Ser missense NM_001408407.1:c.1924G>A NP_001395336.1:p.Gly642Ser missense NM_001408408.1:c.1924G>A NP_001395337.1:p.Gly642Ser missense NM_001408409.1:c.1921G>A NP_001395338.1:p.Gly641Ser missense NM_001408410.1:c.1858G>A NP_001395339.1:p.Gly620Ser missense NM_001408411.1:c.1855G>A NP_001395340.1:p.Gly619Ser missense NM_001408412.1:c.1852G>A NP_001395341.1:p.Gly618Ser missense NM_001408413.1:c.1852G>A NP_001395342.1:p.Gly618Ser missense NM_001408414.1:c.1852G>A NP_001395343.1:p.Gly618Ser missense NM_001408415.1:c.1852G>A NP_001395344.1:p.Gly618Ser missense NM_001408416.1:c.1852G>A NP_001395345.1:p.Gly618Ser missense NM_001408418.1:c.1816G>A NP_001395347.1:p.Gly606Ser missense NM_001408419.1:c.1816G>A NP_001395348.1:p.Gly606Ser missense NM_001408420.1:c.1816G>A NP_001395349.1:p.Gly606Ser missense NM_001408421.1:c.1813G>A NP_001395350.1:p.Gly605Ser missense NM_001408422.1:c.1813G>A NP_001395351.1:p.Gly605Ser missense NM_001408423.1:c.1813G>A NP_001395352.1:p.Gly605Ser missense NM_001408424.1:c.1813G>A NP_001395353.1:p.Gly605Ser missense NM_001408425.1:c.1810G>A NP_001395354.1:p.Gly604Ser missense NM_001408426.1:c.1810G>A NP_001395355.1:p.Gly604Ser missense NM_001408427.1:c.1810G>A NP_001395356.1:p.Gly604Ser missense NM_001408428.1:c.1810G>A NP_001395357.1:p.Gly604Ser missense NM_001408429.1:c.1810G>A NP_001395358.1:p.Gly604Ser missense NM_001408430.1:c.1810G>A NP_001395359.1:p.Gly604Ser missense NM_001408431.1:c.1810G>A NP_001395360.1:p.Gly604Ser missense NM_001408432.1:c.1807G>A NP_001395361.1:p.Gly603Ser missense NM_001408433.1:c.1807G>A NP_001395362.1:p.Gly603Ser missense NM_001408434.1:c.1807G>A NP_001395363.1:p.Gly603Ser missense NM_001408435.1:c.1807G>A NP_001395364.1:p.Gly603Ser missense NM_001408436.1:c.1807G>A NP_001395365.1:p.Gly603Ser missense NM_001408437.1:c.1807G>A NP_001395366.1:p.Gly603Ser missense NM_001408438.1:c.1807G>A NP_001395367.1:p.Gly603Ser missense NM_001408439.1:c.1807G>A NP_001395368.1:p.Gly603Ser missense NM_001408440.1:c.1807G>A NP_001395369.1:p.Gly603Ser missense NM_001408441.1:c.1807G>A NP_001395370.1:p.Gly603Ser missense NM_001408442.1:c.1807G>A NP_001395371.1:p.Gly603Ser missense NM_001408443.1:c.1807G>A NP_001395372.1:p.Gly603Ser missense NM_001408444.1:c.1807G>A NP_001395373.1:p.Gly603Ser missense NM_001408445.1:c.1804G>A NP_001395374.1:p.Gly602Ser missense NM_001408446.1:c.1804G>A NP_001395375.1:p.Gly602Ser missense NM_001408447.1:c.1804G>A NP_001395376.1:p.Gly602Ser missense NM_001408448.1:c.1804G>A NP_001395377.1:p.Gly602Ser missense NM_001408450.1:c.1804G>A NP_001395379.1:p.Gly602Ser missense NM_001408451.1:c.1798G>A NP_001395380.1:p.Gly600Ser missense NM_001408452.1:c.1792G>A NP_001395381.1:p.Gly598Ser missense NM_001408453.1:c.1792G>A NP_001395382.1:p.Gly598Ser missense NM_001408454.1:c.1792G>A NP_001395383.1:p.Gly598Ser missense NM_001408455.1:c.1792G>A NP_001395384.1:p.Gly598Ser missense NM_001408456.1:c.1792G>A NP_001395385.1:p.Gly598Ser missense NM_001408457.1:c.1792G>A NP_001395386.1:p.Gly598Ser missense NM_001408458.1:c.1789G>A NP_001395387.1:p.Gly597Ser missense NM_001408459.1:c.1789G>A NP_001395388.1:p.Gly597Ser missense NM_001408460.1:c.1789G>A NP_001395389.1:p.Gly597Ser missense NM_001408461.1:c.1789G>A NP_001395390.1:p.Gly597Ser missense NM_001408462.1:c.1789G>A NP_001395391.1:p.Gly597Ser missense NM_001408463.1:c.1789G>A NP_001395392.1:p.Gly597Ser missense NM_001408464.1:c.1789G>A NP_001395393.1:p.Gly597Ser missense NM_001408465.1:c.1789G>A NP_001395394.1:p.Gly597Ser missense NM_001408466.1:c.1789G>A NP_001395395.1:p.Gly597Ser missense NM_001408467.1:c.1789G>A NP_001395396.1:p.Gly597Ser missense NM_001408468.1:c.1786G>A NP_001395397.1:p.Gly596Ser missense NM_001408469.1:c.1786G>A NP_001395398.1:p.Gly596Ser missense NM_001408470.1:c.1786G>A NP_001395399.1:p.Gly596Ser missense NM_001408472.1:c.1930G>A NP_001395401.1:p.Gly644Ser missense NM_001408473.1:c.1927G>A NP_001395402.1:p.Gly643Ser missense NM_001408474.1:c.1732G>A NP_001395403.1:p.Gly578Ser missense NM_001408475.1:c.1729G>A NP_001395404.1:p.Gly577Ser missense NM_001408476.1:c.1729G>A NP_001395405.1:p.Gly577Ser missense NM_001408478.1:c.1723G>A NP_001395407.1:p.Gly575Ser missense NM_001408479.1:c.1723G>A NP_001395408.1:p.Gly575Ser missense NM_001408480.1:c.1723G>A NP_001395409.1:p.Gly575Ser missense NM_001408481.1:c.1720G>A NP_001395410.1:p.Gly574Ser missense NM_001408482.1:c.1720G>A NP_001395411.1:p.Gly574Ser missense NM_001408483.1:c.1720G>A NP_001395412.1:p.Gly574Ser missense NM_001408484.1:c.1720G>A NP_001395413.1:p.Gly574Ser missense NM_001408485.1:c.1720G>A NP_001395414.1:p.Gly574Ser missense NM_001408489.1:c.1720G>A NP_001395418.1:p.Gly574Ser missense NM_001408490.1:c.1720G>A NP_001395419.1:p.Gly574Ser missense NM_001408491.1:c.1720G>A NP_001395420.1:p.Gly574Ser missense NM_001408492.1:c.1717G>A NP_001395421.1:p.Gly573Ser missense NM_001408493.1:c.1717G>A NP_001395422.1:p.Gly573Ser missense NM_001408494.1:c.1693G>A NP_001395423.1:p.Gly565Ser missense NM_001408495.1:c.1687G>A NP_001395424.1:p.Gly563Ser missense NM_001408496.1:c.1669G>A NP_001395425.1:p.Gly557Ser missense NM_001408497.1:c.1669G>A NP_001395426.1:p.Gly557Ser missense NM_001408498.1:c.1669G>A NP_001395427.1:p.Gly557Ser missense NM_001408499.1:c.1669G>A NP_001395428.1:p.Gly557Ser missense NM_001408500.1:c.1669G>A NP_001395429.1:p.Gly557Ser missense NM_001408501.1:c.1669G>A NP_001395430.1:p.Gly557Ser missense NM_001408502.1:c.1666G>A NP_001395431.1:p.Gly556Ser missense NM_001408503.1:c.1666G>A NP_001395432.1:p.Gly556Ser missense NM_001408504.1:c.1666G>A NP_001395433.1:p.Gly556Ser missense NM_001408505.1:c.1663G>A NP_001395434.1:p.Gly555Ser missense NM_001408506.1:c.1606G>A NP_001395435.1:p.Gly536Ser missense NM_001408507.1:c.1603G>A NP_001395436.1:p.Gly535Ser missense NM_001408508.1:c.1594G>A NP_001395437.1:p.Gly532Ser missense NM_001408509.1:c.1591G>A NP_001395438.1:p.Gly531Ser missense NM_001408510.1:c.1552G>A NP_001395439.1:p.Gly518Ser missense NM_001408511.1:c.1549G>A NP_001395440.1:p.Gly517Ser missense NM_001408512.1:c.1429G>A NP_001395441.1:p.Gly477Ser missense NM_001408513.1:c.1402G>A NP_001395442.1:p.Gly468Ser missense NM_001408514.1:c.1006G>A NP_001395443.1:p.Gly336Ser missense NM_007297.4:c.5101G>A NP_009228.2:p.Gly1701Ser missense NM_007298.4:c.1930G>A NP_009229.2:p.Gly644Ser missense NM_007299.4:c.1930G>A NP_009230.2:p.Gly644Ser missense NM_007300.4:c.5305G>A NP_009231.2:p.Gly1769Ser missense NM_007304.2:c.1930G>A NP_009235.2:p.Gly644Ser missense NR_027676.2:n.5419G>A non-coding transcript variant NC_000017.11:g.43057087C>T NC_000017.10:g.41209104C>T NG_005905.2:g.160897G>A LRG_292:g.160897G>A LRG_292t1:c.5242G>A LRG_292p1:p.Gly1748Ser - Protein change
- G1748S, G1701S, G1769S, G644S, G1594S, G1620S, G1621S, G1636S, G1637S, G1676S, G1706S, G1720S, G1729S, G1746S, G336S, G477S, G536S, G600S, G605S, G606S, G620S, G642S, G1452S, G1579S, G1619S, G1635S, G1677S, G1721S, G1743S, G1744S, G555S, G573S, G574S, G577S, G598S, G604S, G619S, G666S, G1451S, G1658S, G1659S, G1660S, G1678S, G1680S, G1681S, G1699S, G1700S, G1707S, G1728S, G1768S, G1770S, G517S, G531S, G532S, G535S, G557S, G565S, G575S, G597S, G603S, G641S, G645S, G667S, G880S, G1679S, G1704S, G1705S, G1722S, G1745S, G1747S, G468S, G518S, G556S, G563S, G578S, G596S, G602S, G618S, G643S, G879S
- Other names
- -
- Canonical SPDI
- NC_000017.11:43057086:C: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.5242G>A, a MISSENSE variant, produced a function score of -0.38, 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
|
- | RCV000577664.2 | |
| not provided (1) |
no classification provided
|
- | RCV001076669.3 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 12, 2021 | RCV002336198.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 7, 2024 | RCV003529970.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Apr 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002642489.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Uncertain significance
(Jan 07, 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: SCV004297791.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1748 of the BRCA1 protein (p.Gly1748Ser). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1748 of the BRCA1 protein (p.Gly1748Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 20638108). ClinVar contains an entry for this variant (Variation ID: 55475). 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 with a negative predictive value of 95%. 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)
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679628.1
First in ClinVar: Jan 25, 2018 Last updated: Jan 25, 2018 |
|
|
|
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: SCV001242459.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.375461918556085
|
Comment:
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1748 of the BRCA1 protein (p.Gly1748Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 20638108). ClinVar contains an entry for this variant (Variation ID: 55475). 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 with a negative predictive value of 95%. 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.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001242459.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5242G>A, a MISSENSE variant, produced a function score of -0.38, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5242G>A, a MISSENSE variant, produced a function score of -0.38, 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:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1748 of the BRCA1 protein (p.Gly1748Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 20638108). ClinVar contains an entry for this variant (Variation ID: 55475). 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 with a negative predictive value of 95%. 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
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| Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Identification of point mutations and large rearrangements in the BRCA1 gene in 667 Turkish unselected ovarian cancer patients. | Aktas D | Gynecologic oncology | 2010 | PMID: 20638108 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs397507245 ...
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.