. According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PS3 (strong pathogenic): Reported by three calibrated studies to affect protein function similar to pathogenic control variants (PMIDs:30209399, 32546644, 30765603) (PS3 met)., PM2 (supporting pathogenic): Absent from gnomAD, PP3 (supporting pathogenic): CADD:27.7 REVEL: 0.773 HCI prior:0.81 BayesDEL:0.360228 spliceAI:BRCA1:0.0
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5228G>A (p.Gly1743Glu)
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.
Likely pathogenic
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.5228G>A (p.Gly1743Glu)
Variation ID: 867253 Accession: VCV000867253.3
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43057101 (GRCh38) [ NCBI UCSC ] 17: 41209118 (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 Jan 26, 2024 Jan 9, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5228G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gly1743Glu missense NM_001407571.1:c.5015G>A NP_001394500.1:p.Gly1672Glu missense NM_001407581.1:c.5294G>A NP_001394510.1:p.Gly1765Glu missense NM_001407582.1:c.5294G>A NP_001394511.1:p.Gly1765Glu missense NM_001407583.1:c.5291G>A NP_001394512.1:p.Gly1764Glu missense NM_001407585.1:c.5291G>A NP_001394514.1:p.Gly1764Glu missense NM_001407587.1:c.5291G>A NP_001394516.1:p.Gly1764Glu missense NM_001407590.1:c.5288G>A NP_001394519.1:p.Gly1763Glu missense NM_001407591.1:c.5288G>A NP_001394520.1:p.Gly1763Glu missense NM_001407593.1:c.5228G>A NP_001394522.1:p.Gly1743Glu missense NM_001407594.1:c.5228G>A NP_001394523.1:p.Gly1743Glu missense NM_001407596.1:c.5228G>A NP_001394525.1:p.Gly1743Glu missense NM_001407597.1:c.5228G>A NP_001394526.1:p.Gly1743Glu missense NM_001407598.1:c.5228G>A NP_001394527.1:p.Gly1743Glu missense NM_001407602.1:c.5228G>A NP_001394531.1:p.Gly1743Glu missense NM_001407603.1:c.5228G>A NP_001394532.1:p.Gly1743Glu missense NM_001407605.1:c.5228G>A NP_001394534.1:p.Gly1743Glu missense NM_001407610.1:c.5225G>A NP_001394539.1:p.Gly1742Glu missense NM_001407611.1:c.5225G>A NP_001394540.1:p.Gly1742Glu missense NM_001407612.1:c.5225G>A NP_001394541.1:p.Gly1742Glu missense NM_001407613.1:c.5225G>A NP_001394542.1:p.Gly1742Glu missense NM_001407614.1:c.5225G>A NP_001394543.1:p.Gly1742Glu missense NM_001407615.1:c.5225G>A NP_001394544.1:p.Gly1742Glu missense NM_001407616.1:c.5225G>A NP_001394545.1:p.Gly1742Glu missense NM_001407617.1:c.5225G>A NP_001394546.1:p.Gly1742Glu missense NM_001407618.1:c.5225G>A NP_001394547.1:p.Gly1742Glu missense NM_001407619.1:c.5225G>A NP_001394548.1:p.Gly1742Glu missense NM_001407620.1:c.5225G>A NP_001394549.1:p.Gly1742Glu missense NM_001407621.1:c.5225G>A NP_001394550.1:p.Gly1742Glu missense NM_001407622.1:c.5225G>A NP_001394551.1:p.Gly1742Glu missense NM_001407623.1:c.5225G>A NP_001394552.1:p.Gly1742Glu missense NM_001407624.1:c.5225G>A NP_001394553.1:p.Gly1742Glu missense NM_001407625.1:c.5225G>A NP_001394554.1:p.Gly1742Glu missense NM_001407626.1:c.5225G>A NP_001394555.1:p.Gly1742Glu missense NM_001407627.1:c.5222G>A NP_001394556.1:p.Gly1741Glu missense NM_001407628.1:c.5222G>A NP_001394557.1:p.Gly1741Glu missense NM_001407629.1:c.5222G>A NP_001394558.1:p.Gly1741Glu missense NM_001407630.1:c.5222G>A NP_001394559.1:p.Gly1741Glu missense NM_001407631.1:c.5222G>A NP_001394560.1:p.Gly1741Glu missense NM_001407632.1:c.5222G>A NP_001394561.1:p.Gly1741Glu missense NM_001407633.1:c.5222G>A NP_001394562.1:p.Gly1741Glu missense NM_001407634.1:c.5222G>A NP_001394563.1:p.Gly1741Glu missense NM_001407635.1:c.5222G>A NP_001394564.1:p.Gly1741Glu missense NM_001407636.1:c.5222G>A NP_001394565.1:p.Gly1741Glu missense NM_001407637.1:c.5222G>A NP_001394566.1:p.Gly1741Glu missense NM_001407638.1:c.5222G>A NP_001394567.1:p.Gly1741Glu missense NM_001407639.1:c.5222G>A NP_001394568.1:p.Gly1741Glu missense NM_001407640.1:c.5222G>A NP_001394569.1:p.Gly1741Glu missense NM_001407641.1:c.5222G>A NP_001394570.1:p.Gly1741Glu missense NM_001407642.1:c.5222G>A NP_001394571.1:p.Gly1741Glu missense NM_001407644.1:c.5219G>A NP_001394573.1:p.Gly1740Glu missense NM_001407645.1:c.5219G>A NP_001394574.1:p.Gly1740Glu missense NM_001407646.1:c.5216G>A NP_001394575.1:p.Gly1739Glu missense NM_001407647.1:c.5213G>A NP_001394576.1:p.Gly1738Glu missense NM_001407648.1:c.5171G>A NP_001394577.1:p.Gly1724Glu missense NM_001407649.1:c.5168G>A NP_001394578.1:p.Gly1723Glu missense NM_001407652.1:c.5150G>A NP_001394581.1:p.Gly1717Glu missense NM_001407653.1:c.5150G>A NP_001394582.1:p.Gly1717Glu missense NM_001407654.1:c.5150G>A NP_001394583.1:p.Gly1717Glu missense NM_001407655.1:c.5150G>A NP_001394584.1:p.Gly1717Glu missense NM_001407656.1:c.5147G>A NP_001394585.1:p.Gly1716Glu missense NM_001407657.1:c.5147G>A NP_001394586.1:p.Gly1716Glu missense NM_001407658.1:c.5147G>A NP_001394587.1:p.Gly1716Glu missense NM_001407659.1:c.5144G>A NP_001394588.1:p.Gly1715Glu missense NM_001407660.1:c.5144G>A NP_001394589.1:p.Gly1715Glu missense NM_001407661.1:c.5144G>A NP_001394590.1:p.Gly1715Glu missense NM_001407662.1:c.5144G>A NP_001394591.1:p.Gly1715Glu missense NM_001407663.1:c.5144G>A NP_001394592.1:p.Gly1715Glu missense NM_001407664.1:c.5105G>A NP_001394593.1:p.Gly1702Glu missense NM_001407665.1:c.5105G>A NP_001394594.1:p.Gly1702Glu missense NM_001407666.1:c.5105G>A NP_001394595.1:p.Gly1702Glu missense NM_001407667.1:c.5105G>A NP_001394596.1:p.Gly1702Glu missense NM_001407668.1:c.5105G>A NP_001394597.1:p.Gly1702Glu missense NM_001407669.1:c.5105G>A NP_001394598.1:p.Gly1702Glu missense NM_001407670.1:c.5102G>A NP_001394599.1:p.Gly1701Glu missense NM_001407671.1:c.5102G>A NP_001394600.1:p.Gly1701Glu missense NM_001407672.1:c.5102G>A NP_001394601.1:p.Gly1701Glu missense NM_001407673.1:c.5102G>A NP_001394602.1:p.Gly1701Glu missense NM_001407674.1:c.5102G>A NP_001394603.1:p.Gly1701Glu missense NM_001407675.1:c.5102G>A NP_001394604.1:p.Gly1701Glu missense NM_001407676.1:c.5102G>A NP_001394605.1:p.Gly1701Glu missense NM_001407677.1:c.5102G>A NP_001394606.1:p.Gly1701Glu missense NM_001407678.1:c.5102G>A NP_001394607.1:p.Gly1701Glu missense NM_001407679.1:c.5102G>A NP_001394608.1:p.Gly1701Glu missense NM_001407680.1:c.5102G>A NP_001394609.1:p.Gly1701Glu missense NM_001407681.1:c.5099G>A NP_001394610.1:p.Gly1700Glu missense NM_001407682.1:c.5099G>A NP_001394611.1:p.Gly1700Glu missense NM_001407683.1:c.5099G>A NP_001394612.1:p.Gly1700Glu missense NM_001407684.1:c.5228G>A NP_001394613.1:p.Gly1743Glu missense NM_001407685.1:c.5099G>A NP_001394614.1:p.Gly1700Glu missense NM_001407686.1:c.5099G>A NP_001394615.1:p.Gly1700Glu missense NM_001407687.1:c.5099G>A NP_001394616.1:p.Gly1700Glu missense NM_001407688.1:c.5099G>A NP_001394617.1:p.Gly1700Glu missense NM_001407689.1:c.5099G>A NP_001394618.1:p.Gly1700Glu missense NM_001407690.1:c.5096G>A NP_001394619.1:p.Gly1699Glu missense NM_001407691.1:c.5096G>A NP_001394620.1:p.Gly1699Glu missense NM_001407692.1:c.5087G>A NP_001394621.1:p.Gly1696Glu missense NM_001407694.1:c.5087G>A NP_001394623.1:p.Gly1696Glu missense NM_001407695.1:c.5087G>A NP_001394624.1:p.Gly1696Glu missense NM_001407696.1:c.5087G>A NP_001394625.1:p.Gly1696Glu missense NM_001407697.1:c.5087G>A NP_001394626.1:p.Gly1696Glu missense NM_001407698.1:c.5087G>A NP_001394627.1:p.Gly1696Glu missense NM_001407724.1:c.5087G>A NP_001394653.1:p.Gly1696Glu missense NM_001407725.1:c.5087G>A NP_001394654.1:p.Gly1696Glu missense NM_001407726.1:c.5087G>A NP_001394655.1:p.Gly1696Glu missense NM_001407727.1:c.5087G>A NP_001394656.1:p.Gly1696Glu missense NM_001407728.1:c.5087G>A NP_001394657.1:p.Gly1696Glu missense NM_001407729.1:c.5087G>A NP_001394658.1:p.Gly1696Glu missense NM_001407730.1:c.5087G>A NP_001394659.1:p.Gly1696Glu missense NM_001407731.1:c.5087G>A NP_001394660.1:p.Gly1696Glu missense NM_001407732.1:c.5084G>A NP_001394661.1:p.Gly1695Glu missense NM_001407733.1:c.5084G>A NP_001394662.1:p.Gly1695Glu missense NM_001407734.1:c.5084G>A NP_001394663.1:p.Gly1695Glu missense NM_001407735.1:c.5084G>A NP_001394664.1:p.Gly1695Glu missense NM_001407736.1:c.5084G>A NP_001394665.1:p.Gly1695Glu missense NM_001407737.1:c.5084G>A NP_001394666.1:p.Gly1695Glu missense NM_001407738.1:c.5084G>A NP_001394667.1:p.Gly1695Glu missense NM_001407739.1:c.5084G>A NP_001394668.1:p.Gly1695Glu missense NM_001407740.1:c.5084G>A NP_001394669.1:p.Gly1695Glu missense NM_001407741.1:c.5084G>A NP_001394670.1:p.Gly1695Glu missense NM_001407742.1:c.5084G>A NP_001394671.1:p.Gly1695Glu missense NM_001407743.1:c.5084G>A NP_001394672.1:p.Gly1695Glu missense NM_001407744.1:c.5084G>A NP_001394673.1:p.Gly1695Glu missense NM_001407745.1:c.5084G>A NP_001394674.1:p.Gly1695Glu missense NM_001407746.1:c.5084G>A NP_001394675.1:p.Gly1695Glu missense NM_001407747.1:c.5084G>A NP_001394676.1:p.Gly1695Glu missense NM_001407748.1:c.5084G>A NP_001394677.1:p.Gly1695Glu missense NM_001407749.1:c.5084G>A NP_001394678.1:p.Gly1695Glu missense NM_001407750.1:c.5084G>A NP_001394679.1:p.Gly1695Glu missense NM_001407751.1:c.5084G>A NP_001394680.1:p.Gly1695Glu missense NM_001407752.1:c.5084G>A NP_001394681.1:p.Gly1695Glu missense NM_001407838.1:c.5081G>A NP_001394767.1:p.Gly1694Glu missense NM_001407839.1:c.5081G>A NP_001394768.1:p.Gly1694Glu missense NM_001407841.1:c.5081G>A NP_001394770.1:p.Gly1694Glu missense NM_001407842.1:c.5081G>A NP_001394771.1:p.Gly1694Glu missense NM_001407843.1:c.5081G>A NP_001394772.1:p.Gly1694Glu missense NM_001407844.1:c.5081G>A NP_001394773.1:p.Gly1694Glu missense NM_001407845.1:c.5081G>A NP_001394774.1:p.Gly1694Glu missense NM_001407846.1:c.5081G>A NP_001394775.1:p.Gly1694Glu missense NM_001407847.1:c.5081G>A NP_001394776.1:p.Gly1694Glu missense NM_001407848.1:c.5081G>A NP_001394777.1:p.Gly1694Glu missense NM_001407849.1:c.5081G>A NP_001394778.1:p.Gly1694Glu missense NM_001407850.1:c.5081G>A NP_001394779.1:p.Gly1694Glu missense NM_001407851.1:c.5081G>A NP_001394780.1:p.Gly1694Glu missense NM_001407852.1:c.5081G>A NP_001394781.1:p.Gly1694Glu missense NM_001407853.1:c.5081G>A NP_001394782.1:p.Gly1694Glu missense NM_001407854.1:c.5228G>A NP_001394783.1:p.Gly1743Glu missense NM_001407858.1:c.5225G>A NP_001394787.1:p.Gly1742Glu missense NM_001407859.1:c.5225G>A NP_001394788.1:p.Gly1742Glu missense NM_001407860.1:c.5225G>A NP_001394789.1:p.Gly1742Glu missense NM_001407861.1:c.5222G>A NP_001394790.1:p.Gly1741Glu missense NM_001407862.1:c.5027G>A NP_001394791.1:p.Gly1676Glu missense NM_001407863.1:c.5024G>A NP_001394792.1:p.Gly1675Glu missense NM_001407874.1:c.5021G>A NP_001394803.1:p.Gly1674Glu missense NM_001407875.1:c.5021G>A NP_001394804.1:p.Gly1674Glu missense NM_001407879.1:c.5018G>A NP_001394808.1:p.Gly1673Glu missense NM_001407881.1:c.5018G>A NP_001394810.1:p.Gly1673Glu missense NM_001407882.1:c.5018G>A NP_001394811.1:p.Gly1673Glu missense NM_001407884.1:c.5018G>A NP_001394813.1:p.Gly1673Glu missense NM_001407885.1:c.5018G>A NP_001394814.1:p.Gly1673Glu missense NM_001407886.1:c.5018G>A NP_001394815.1:p.Gly1673Glu missense NM_001407887.1:c.5018G>A NP_001394816.1:p.Gly1673Glu missense NM_001407889.1:c.5018G>A NP_001394818.1:p.Gly1673Glu missense NM_001407894.1:c.5015G>A NP_001394823.1:p.Gly1672Glu missense NM_001407895.1:c.5015G>A NP_001394824.1:p.Gly1672Glu missense NM_001407896.1:c.5015G>A NP_001394825.1:p.Gly1672Glu missense NM_001407897.1:c.5015G>A NP_001394826.1:p.Gly1672Glu missense NM_001407898.1:c.5015G>A NP_001394827.1:p.Gly1672Glu missense NM_001407899.1:c.5015G>A NP_001394828.1:p.Gly1672Glu missense NM_001407900.1:c.5015G>A NP_001394829.1:p.Gly1672Glu missense NM_001407902.1:c.5015G>A NP_001394831.1:p.Gly1672Glu missense NM_001407904.1:c.5015G>A NP_001394833.1:p.Gly1672Glu missense NM_001407906.1:c.5015G>A NP_001394835.1:p.Gly1672Glu missense NM_001407907.1:c.5015G>A NP_001394836.1:p.Gly1672Glu missense NM_001407908.1:c.5015G>A NP_001394837.1:p.Gly1672Glu missense NM_001407909.1:c.5015G>A NP_001394838.1:p.Gly1672Glu missense NM_001407910.1:c.5015G>A NP_001394839.1:p.Gly1672Glu missense NM_001407915.1:c.5012G>A NP_001394844.1:p.Gly1671Glu missense NM_001407916.1:c.5012G>A NP_001394845.1:p.Gly1671Glu missense NM_001407917.1:c.5012G>A NP_001394846.1:p.Gly1671Glu missense NM_001407918.1:c.5012G>A NP_001394847.1:p.Gly1671Glu missense NM_001407919.1:c.5105G>A NP_001394848.1:p.Gly1702Glu missense NM_001407920.1:c.4964G>A NP_001394849.1:p.Gly1655Glu missense NM_001407921.1:c.4964G>A NP_001394850.1:p.Gly1655Glu missense NM_001407922.1:c.4964G>A NP_001394851.1:p.Gly1655Glu missense NM_001407923.1:c.4964G>A NP_001394852.1:p.Gly1655Glu missense NM_001407924.1:c.4964G>A NP_001394853.1:p.Gly1655Glu missense NM_001407925.1:c.4964G>A NP_001394854.1:p.Gly1655Glu missense NM_001407926.1:c.4964G>A NP_001394855.1:p.Gly1655Glu missense NM_001407927.1:c.4961G>A NP_001394856.1:p.Gly1654Glu missense NM_001407928.1:c.4961G>A NP_001394857.1:p.Gly1654Glu missense NM_001407929.1:c.4961G>A NP_001394858.1:p.Gly1654Glu missense NM_001407930.1:c.4961G>A NP_001394859.1:p.Gly1654Glu missense NM_001407931.1:c.4961G>A NP_001394860.1:p.Gly1654Glu missense NM_001407932.1:c.4961G>A NP_001394861.1:p.Gly1654Glu missense NM_001407933.1:c.4961G>A NP_001394862.1:p.Gly1654Glu missense NM_001407934.1:c.4958G>A NP_001394863.1:p.Gly1653Glu missense NM_001407935.1:c.4958G>A NP_001394864.1:p.Gly1653Glu missense NM_001407936.1:c.4958G>A NP_001394865.1:p.Gly1653Glu missense NM_001407937.1:c.5105G>A NP_001394866.1:p.Gly1702Glu missense NM_001407938.1:c.5105G>A NP_001394867.1:p.Gly1702Glu missense NM_001407939.1:c.5102G>A NP_001394868.1:p.Gly1701Glu missense NM_001407940.1:c.5102G>A NP_001394869.1:p.Gly1701Glu missense NM_001407941.1:c.5099G>A NP_001394870.1:p.Gly1700Glu missense NM_001407942.1:c.5087G>A NP_001394871.1:p.Gly1696Glu missense NM_001407943.1:c.5084G>A NP_001394872.1:p.Gly1695Glu missense NM_001407944.1:c.5084G>A NP_001394873.1:p.Gly1695Glu missense NM_001407945.1:c.5084G>A NP_001394874.1:p.Gly1695Glu missense NM_001407946.1:c.4895G>A NP_001394875.1:p.Gly1632Glu missense NM_001407947.1:c.4895G>A NP_001394876.1:p.Gly1632Glu missense NM_001407948.1:c.4895G>A NP_001394877.1:p.Gly1632Glu missense NM_001407949.1:c.4895G>A NP_001394878.1:p.Gly1632Glu missense NM_001407950.1:c.4892G>A NP_001394879.1:p.Gly1631Glu missense NM_001407951.1:c.4892G>A NP_001394880.1:p.Gly1631Glu missense NM_001407952.1:c.4892G>A NP_001394881.1:p.Gly1631Glu missense NM_001407953.1:c.4892G>A NP_001394882.1:p.Gly1631Glu missense NM_001407954.1:c.4892G>A NP_001394883.1:p.Gly1631Glu missense NM_001407955.1:c.4892G>A NP_001394884.1:p.Gly1631Glu missense NM_001407956.1:c.4889G>A NP_001394885.1:p.Gly1630Glu missense NM_001407957.1:c.4889G>A NP_001394886.1:p.Gly1630Glu missense NM_001407958.1:c.4889G>A NP_001394887.1:p.Gly1630Glu missense NM_001407959.1:c.4847G>A NP_001394888.1:p.Gly1616Glu missense NM_001407960.1:c.4844G>A NP_001394889.1:p.Gly1615Glu missense NM_001407962.1:c.4844G>A NP_001394891.1:p.Gly1615Glu missense NM_001407963.1:c.4841G>A NP_001394892.1:p.Gly1614Glu missense NM_001407964.1:c.4766G>A NP_001394893.1:p.Gly1589Glu missense NM_001407965.1:c.4721G>A NP_001394894.1:p.Gly1574Glu missense NM_001407966.1:c.4340G>A NP_001394895.1:p.Gly1447Glu missense NM_001407967.1:c.4337G>A NP_001394896.1:p.Gly1446Glu missense NM_001407968.1:c.2624G>A NP_001394897.1:p.Gly875Glu missense NM_001407969.1:c.2621G>A NP_001394898.1:p.Gly874Glu missense NM_001407970.1:c.1985G>A NP_001394899.1:p.Gly662Glu missense NM_001407971.1:c.1985G>A NP_001394900.1:p.Gly662Glu missense NM_001407972.1:c.1982G>A NP_001394901.1:p.Gly661Glu missense NM_001407973.1:c.1919G>A NP_001394902.1:p.Gly640Glu missense NM_001407974.1:c.1919G>A NP_001394903.1:p.Gly640Glu missense NM_001407975.1:c.1919G>A NP_001394904.1:p.Gly640Glu missense NM_001407976.1:c.1919G>A NP_001394905.1:p.Gly640Glu missense NM_001407977.1:c.1919G>A NP_001394906.1:p.Gly640Glu missense NM_001407978.1:c.1919G>A NP_001394907.1:p.Gly640Glu missense NM_001407979.1:c.1916G>A NP_001394908.1:p.Gly639Glu missense NM_001407980.1:c.1916G>A NP_001394909.1:p.Gly639Glu missense NM_001407981.1:c.1916G>A NP_001394910.1:p.Gly639Glu missense NM_001407982.1:c.1916G>A NP_001394911.1:p.Gly639Glu missense NM_001407983.1:c.1916G>A NP_001394912.1:p.Gly639Glu missense NM_001407984.1:c.1916G>A NP_001394913.1:p.Gly639Glu missense NM_001407985.1:c.1916G>A NP_001394914.1:p.Gly639Glu missense NM_001407986.1:c.1916G>A NP_001394915.1:p.Gly639Glu missense NM_001407990.1:c.1916G>A NP_001394919.1:p.Gly639Glu missense NM_001407991.1:c.1916G>A NP_001394920.1:p.Gly639Glu missense NM_001407992.1:c.1916G>A NP_001394921.1:p.Gly639Glu missense NM_001407993.1:c.1916G>A NP_001394922.1:p.Gly639Glu missense NM_001408392.1:c.1913G>A NP_001395321.1:p.Gly638Glu missense NM_001408396.1:c.1913G>A NP_001395325.1:p.Gly638Glu missense NM_001408397.1:c.1913G>A NP_001395326.1:p.Gly638Glu missense NM_001408398.1:c.1913G>A NP_001395327.1:p.Gly638Glu missense NM_001408399.1:c.1913G>A NP_001395328.1:p.Gly638Glu missense NM_001408400.1:c.1913G>A NP_001395329.1:p.Gly638Glu missense NM_001408401.1:c.1913G>A NP_001395330.1:p.Gly638Glu missense NM_001408402.1:c.1913G>A NP_001395331.1:p.Gly638Glu missense NM_001408403.1:c.1913G>A NP_001395332.1:p.Gly638Glu missense NM_001408404.1:c.1913G>A NP_001395333.1:p.Gly638Glu missense NM_001408406.1:c.1910G>A NP_001395335.1:p.Gly637Glu missense NM_001408407.1:c.1910G>A NP_001395336.1:p.Gly637Glu missense NM_001408408.1:c.1910G>A NP_001395337.1:p.Gly637Glu missense NM_001408409.1:c.1907G>A NP_001395338.1:p.Gly636Glu missense NM_001408410.1:c.1844G>A NP_001395339.1:p.Gly615Glu missense NM_001408411.1:c.1841G>A NP_001395340.1:p.Gly614Glu missense NM_001408412.1:c.1838G>A NP_001395341.1:p.Gly613Glu missense NM_001408413.1:c.1838G>A NP_001395342.1:p.Gly613Glu missense NM_001408414.1:c.1838G>A NP_001395343.1:p.Gly613Glu missense NM_001408415.1:c.1838G>A NP_001395344.1:p.Gly613Glu missense NM_001408416.1:c.1838G>A NP_001395345.1:p.Gly613Glu missense NM_001408418.1:c.1802G>A NP_001395347.1:p.Gly601Glu missense NM_001408419.1:c.1802G>A NP_001395348.1:p.Gly601Glu missense NM_001408420.1:c.1802G>A NP_001395349.1:p.Gly601Glu missense NM_001408421.1:c.1799G>A NP_001395350.1:p.Gly600Glu missense NM_001408422.1:c.1799G>A NP_001395351.1:p.Gly600Glu missense NM_001408423.1:c.1799G>A NP_001395352.1:p.Gly600Glu missense NM_001408424.1:c.1799G>A NP_001395353.1:p.Gly600Glu missense NM_001408425.1:c.1796G>A NP_001395354.1:p.Gly599Glu missense NM_001408426.1:c.1796G>A NP_001395355.1:p.Gly599Glu missense NM_001408427.1:c.1796G>A NP_001395356.1:p.Gly599Glu missense NM_001408428.1:c.1796G>A NP_001395357.1:p.Gly599Glu missense NM_001408429.1:c.1796G>A NP_001395358.1:p.Gly599Glu missense NM_001408430.1:c.1796G>A NP_001395359.1:p.Gly599Glu missense NM_001408431.1:c.1796G>A NP_001395360.1:p.Gly599Glu missense NM_001408432.1:c.1793G>A NP_001395361.1:p.Gly598Glu missense NM_001408433.1:c.1793G>A NP_001395362.1:p.Gly598Glu missense NM_001408434.1:c.1793G>A NP_001395363.1:p.Gly598Glu missense NM_001408435.1:c.1793G>A NP_001395364.1:p.Gly598Glu missense NM_001408436.1:c.1793G>A NP_001395365.1:p.Gly598Glu missense NM_001408437.1:c.1793G>A NP_001395366.1:p.Gly598Glu missense NM_001408438.1:c.1793G>A NP_001395367.1:p.Gly598Glu missense NM_001408439.1:c.1793G>A NP_001395368.1:p.Gly598Glu missense NM_001408440.1:c.1793G>A NP_001395369.1:p.Gly598Glu missense NM_001408441.1:c.1793G>A NP_001395370.1:p.Gly598Glu missense NM_001408442.1:c.1793G>A NP_001395371.1:p.Gly598Glu missense NM_001408443.1:c.1793G>A NP_001395372.1:p.Gly598Glu missense NM_001408444.1:c.1793G>A NP_001395373.1:p.Gly598Glu missense NM_001408445.1:c.1790G>A NP_001395374.1:p.Gly597Glu missense NM_001408446.1:c.1790G>A NP_001395375.1:p.Gly597Glu missense NM_001408447.1:c.1790G>A NP_001395376.1:p.Gly597Glu missense NM_001408448.1:c.1790G>A NP_001395377.1:p.Gly597Glu missense NM_001408450.1:c.1790G>A NP_001395379.1:p.Gly597Glu missense NM_001408451.1:c.1784G>A NP_001395380.1:p.Gly595Glu missense NM_001408452.1:c.1778G>A NP_001395381.1:p.Gly593Glu missense NM_001408453.1:c.1778G>A NP_001395382.1:p.Gly593Glu missense NM_001408454.1:c.1778G>A NP_001395383.1:p.Gly593Glu missense NM_001408455.1:c.1778G>A NP_001395384.1:p.Gly593Glu missense NM_001408456.1:c.1778G>A NP_001395385.1:p.Gly593Glu missense NM_001408457.1:c.1778G>A NP_001395386.1:p.Gly593Glu missense NM_001408458.1:c.1775G>A NP_001395387.1:p.Gly592Glu missense NM_001408459.1:c.1775G>A NP_001395388.1:p.Gly592Glu missense NM_001408460.1:c.1775G>A NP_001395389.1:p.Gly592Glu missense NM_001408461.1:c.1775G>A NP_001395390.1:p.Gly592Glu missense NM_001408462.1:c.1775G>A NP_001395391.1:p.Gly592Glu missense NM_001408463.1:c.1775G>A NP_001395392.1:p.Gly592Glu missense NM_001408464.1:c.1775G>A NP_001395393.1:p.Gly592Glu missense NM_001408465.1:c.1775G>A NP_001395394.1:p.Gly592Glu missense NM_001408466.1:c.1775G>A NP_001395395.1:p.Gly592Glu missense NM_001408467.1:c.1775G>A NP_001395396.1:p.Gly592Glu missense NM_001408468.1:c.1772G>A NP_001395397.1:p.Gly591Glu missense NM_001408469.1:c.1772G>A NP_001395398.1:p.Gly591Glu missense NM_001408470.1:c.1772G>A NP_001395399.1:p.Gly591Glu missense NM_001408472.1:c.1916G>A NP_001395401.1:p.Gly639Glu missense NM_001408473.1:c.1913G>A NP_001395402.1:p.Gly638Glu missense NM_001408474.1:c.1718G>A NP_001395403.1:p.Gly573Glu missense NM_001408475.1:c.1715G>A NP_001395404.1:p.Gly572Glu missense NM_001408476.1:c.1715G>A NP_001395405.1:p.Gly572Glu missense NM_001408478.1:c.1709G>A NP_001395407.1:p.Gly570Glu missense NM_001408479.1:c.1709G>A NP_001395408.1:p.Gly570Glu missense NM_001408480.1:c.1709G>A NP_001395409.1:p.Gly570Glu missense NM_001408481.1:c.1706G>A NP_001395410.1:p.Gly569Glu missense NM_001408482.1:c.1706G>A NP_001395411.1:p.Gly569Glu missense NM_001408483.1:c.1706G>A NP_001395412.1:p.Gly569Glu missense NM_001408484.1:c.1706G>A NP_001395413.1:p.Gly569Glu missense NM_001408485.1:c.1706G>A NP_001395414.1:p.Gly569Glu missense NM_001408489.1:c.1706G>A NP_001395418.1:p.Gly569Glu missense NM_001408490.1:c.1706G>A NP_001395419.1:p.Gly569Glu missense NM_001408491.1:c.1706G>A NP_001395420.1:p.Gly569Glu missense NM_001408492.1:c.1703G>A NP_001395421.1:p.Gly568Glu missense NM_001408493.1:c.1703G>A NP_001395422.1:p.Gly568Glu missense NM_001408494.1:c.1679G>A NP_001395423.1:p.Gly560Glu missense NM_001408495.1:c.1673G>A NP_001395424.1:p.Gly558Glu missense NM_001408496.1:c.1655G>A NP_001395425.1:p.Gly552Glu missense NM_001408497.1:c.1655G>A NP_001395426.1:p.Gly552Glu missense NM_001408498.1:c.1655G>A NP_001395427.1:p.Gly552Glu missense NM_001408499.1:c.1655G>A NP_001395428.1:p.Gly552Glu missense NM_001408500.1:c.1655G>A NP_001395429.1:p.Gly552Glu missense NM_001408501.1:c.1655G>A NP_001395430.1:p.Gly552Glu missense NM_001408502.1:c.1652G>A NP_001395431.1:p.Gly551Glu missense NM_001408503.1:c.1652G>A NP_001395432.1:p.Gly551Glu missense NM_001408504.1:c.1652G>A NP_001395433.1:p.Gly551Glu missense NM_001408505.1:c.1649G>A NP_001395434.1:p.Gly550Glu missense NM_001408506.1:c.1592G>A NP_001395435.1:p.Gly531Glu missense NM_001408507.1:c.1589G>A NP_001395436.1:p.Gly530Glu missense NM_001408508.1:c.1580G>A NP_001395437.1:p.Gly527Glu missense NM_001408509.1:c.1577G>A NP_001395438.1:p.Gly526Glu missense NM_001408510.1:c.1538G>A NP_001395439.1:p.Gly513Glu missense NM_001408511.1:c.1535G>A NP_001395440.1:p.Gly512Glu missense NM_001408512.1:c.1415G>A NP_001395441.1:p.Gly472Glu missense NM_001408513.1:c.1388G>A NP_001395442.1:p.Gly463Glu missense NM_001408514.1:c.992G>A NP_001395443.1:p.Gly331Glu missense NM_007297.4:c.5087G>A NP_009228.2:p.Gly1696Glu missense NM_007298.4:c.1916G>A NP_009229.2:p.Gly639Glu missense NM_007299.4:c.1916G>A NP_009230.2:p.Gly639Glu missense NM_007300.4:c.5291G>A NP_009231.2:p.Gly1764Glu missense NM_007304.2:c.1916G>A NP_009235.2:p.Gly639Glu missense NR_027676.2:n.5405G>A non-coding transcript variant NC_000017.11:g.43057101C>T NC_000017.10:g.41209118C>T NG_005905.2:g.160883G>A LRG_292:g.160883G>A LRG_292t1:c.5228G>A LRG_292p1:p.Gly1743Glu - Protein change
- G1743E, G1696E, G1764E, G639E, G1447E, G1574E, G1630E, G1632E, G1676E, G1700E, G1702E, G1715E, G1716E, G1740E, G463E, G593E, G595E, G597E, G615E, G636E, G637E, G875E, G1589E, G1616E, G1655E, G1675E, G1701E, G1724E, G1738E, G1742E, G331E, G472E, G513E, G530E, G550E, G551E, G569E, G572E, G573E, G591E, G599E, G614E, G638E, G640E, G1446E, G1614E, G1631E, G1653E, G1654E, G1671E, G1672E, G1674E, G1699E, G1723E, G1741E, G1765E, G531E, G558E, G570E, G600E, G601E, G613E, G661E, G874E, G1615E, G1673E, G1694E, G1695E, G1717E, G1739E, G1763E, G512E, G526E, G527E, G552E, G560E, G568E, G592E, G598E, G662E
- Other names
- -
- Canonical SPDI
- NC_000017.11:43057100: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.5228G>A, a MISSENSE variant, produced a function score of -2.83, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| not provided (1) |
no classification provided
|
- | RCV001075901.3 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jan 9, 2024 | RCV003483779.1 |
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 pathogenic
(Jan 09, 2024)
|
criteria provided, single submitter
Method: curation
|
Hereditary breast ovarian cancer syndrome
Affected status: not provided
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV004231853.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
. According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PS3 (strong pathogenic): Reported by three calibrated studies to affect protein function … (more)
. According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PS3 (strong pathogenic): Reported by three calibrated studies to affect protein function similar to pathogenic control variants (PMIDs:30209399, 32546644, 30765603) (PS3 met)., PM2 (supporting pathogenic): Absent from gnomAD, PP3 (supporting pathogenic): CADD:27.7 REVEL: 0.773 HCI prior:0.81 BayesDEL:0.360228 spliceAI:BRCA1:0.0 (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: SCV001241553.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.83110591414681
|
Comment:
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
functionally_abnormal
|
Method citation(s):
|
|
Brotman Baty Institute, University of Washington
Accession: SCV001241553.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5228G>A, a MISSENSE variant, produced a function score of -2.83, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5228G>A, a MISSENSE variant, produced a function score of -2.83, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
|
Comment:
. According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PS3 (strong pathogenic): Reported by three calibrated studies to affect protein function similar to pathogenic control variants (PMIDs:30209399, 32546644, 30765603) (PS3 met)., PM2 (supporting pathogenic): Absent from gnomAD, PP3 (supporting pathogenic): CADD:27.7 REVEL: 0.773 HCI prior:0.81 BayesDEL:0.360228 spliceAI:BRCA1:0.0
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 rs1346819781 ...
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Record last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.