Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.3847C>T (p.His1283Tyr)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)
Uncertain significance(1); Likely benign(1)
2
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.3847C>T (p.His1283Tyr)
Variation ID: 441432 Accession: VCV000441432.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091684 (GRCh38) [ NCBI UCSC ] 17: 41243701 (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 Oct 23, 2017 May 1, 2024 Mar 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.3847C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.His1283Tyr missense NM_001407571.1:c.3634C>T NP_001394500.1:p.His1212Tyr missense NM_001407581.1:c.3847C>T NP_001394510.1:p.His1283Tyr missense NM_001407582.1:c.3847C>T NP_001394511.1:p.His1283Tyr missense NM_001407583.1:c.3847C>T NP_001394512.1:p.His1283Tyr missense NM_001407585.1:c.3847C>T NP_001394514.1:p.His1283Tyr missense NM_001407587.1:c.3844C>T NP_001394516.1:p.His1282Tyr missense NM_001407590.1:c.3844C>T NP_001394519.1:p.His1282Tyr missense NM_001407591.1:c.3844C>T NP_001394520.1:p.His1282Tyr missense NM_001407593.1:c.3847C>T NP_001394522.1:p.His1283Tyr missense NM_001407594.1:c.3847C>T NP_001394523.1:p.His1283Tyr missense NM_001407596.1:c.3847C>T NP_001394525.1:p.His1283Tyr missense NM_001407597.1:c.3847C>T NP_001394526.1:p.His1283Tyr missense NM_001407598.1:c.3847C>T NP_001394527.1:p.His1283Tyr missense NM_001407602.1:c.3847C>T NP_001394531.1:p.His1283Tyr missense NM_001407603.1:c.3847C>T NP_001394532.1:p.His1283Tyr missense NM_001407605.1:c.3847C>T NP_001394534.1:p.His1283Tyr missense NM_001407610.1:c.3844C>T NP_001394539.1:p.His1282Tyr missense NM_001407611.1:c.3844C>T NP_001394540.1:p.His1282Tyr missense NM_001407612.1:c.3844C>T NP_001394541.1:p.His1282Tyr missense NM_001407613.1:c.3844C>T NP_001394542.1:p.His1282Tyr missense NM_001407614.1:c.3844C>T NP_001394543.1:p.His1282Tyr missense NM_001407615.1:c.3844C>T NP_001394544.1:p.His1282Tyr missense NM_001407616.1:c.3847C>T NP_001394545.1:p.His1283Tyr missense NM_001407617.1:c.3847C>T NP_001394546.1:p.His1283Tyr missense NM_001407618.1:c.3847C>T NP_001394547.1:p.His1283Tyr missense NM_001407619.1:c.3847C>T NP_001394548.1:p.His1283Tyr missense NM_001407620.1:c.3847C>T NP_001394549.1:p.His1283Tyr missense NM_001407621.1:c.3847C>T NP_001394550.1:p.His1283Tyr missense NM_001407622.1:c.3847C>T NP_001394551.1:p.His1283Tyr missense NM_001407623.1:c.3847C>T NP_001394552.1:p.His1283Tyr missense NM_001407624.1:c.3847C>T NP_001394553.1:p.His1283Tyr missense NM_001407625.1:c.3847C>T NP_001394554.1:p.His1283Tyr missense NM_001407626.1:c.3847C>T NP_001394555.1:p.His1283Tyr missense NM_001407627.1:c.3844C>T NP_001394556.1:p.His1282Tyr missense NM_001407628.1:c.3844C>T NP_001394557.1:p.His1282Tyr missense NM_001407629.1:c.3844C>T NP_001394558.1:p.His1282Tyr missense NM_001407630.1:c.3844C>T NP_001394559.1:p.His1282Tyr missense NM_001407631.1:c.3844C>T NP_001394560.1:p.His1282Tyr missense NM_001407632.1:c.3844C>T NP_001394561.1:p.His1282Tyr missense NM_001407633.1:c.3844C>T NP_001394562.1:p.His1282Tyr missense NM_001407634.1:c.3844C>T NP_001394563.1:p.His1282Tyr missense NM_001407635.1:c.3844C>T NP_001394564.1:p.His1282Tyr missense NM_001407636.1:c.3844C>T NP_001394565.1:p.His1282Tyr missense NM_001407637.1:c.3844C>T NP_001394566.1:p.His1282Tyr missense NM_001407638.1:c.3844C>T NP_001394567.1:p.His1282Tyr missense NM_001407639.1:c.3847C>T NP_001394568.1:p.His1283Tyr missense NM_001407640.1:c.3847C>T NP_001394569.1:p.His1283Tyr missense NM_001407641.1:c.3847C>T NP_001394570.1:p.His1283Tyr missense NM_001407642.1:c.3847C>T NP_001394571.1:p.His1283Tyr missense NM_001407644.1:c.3844C>T NP_001394573.1:p.His1282Tyr missense NM_001407645.1:c.3844C>T NP_001394574.1:p.His1282Tyr missense NM_001407646.1:c.3838C>T NP_001394575.1:p.His1280Tyr missense NM_001407647.1:c.3838C>T NP_001394576.1:p.His1280Tyr missense NM_001407648.1:c.3724C>T NP_001394577.1:p.His1242Tyr missense NM_001407649.1:c.3721C>T NP_001394578.1:p.His1241Tyr missense NM_001407652.1:c.3847C>T NP_001394581.1:p.His1283Tyr missense NM_001407653.1:c.3769C>T NP_001394582.1:p.His1257Tyr missense NM_001407654.1:c.3769C>T NP_001394583.1:p.His1257Tyr missense NM_001407655.1:c.3769C>T NP_001394584.1:p.His1257Tyr missense NM_001407656.1:c.3769C>T NP_001394585.1:p.His1257Tyr missense NM_001407657.1:c.3769C>T NP_001394586.1:p.His1257Tyr missense NM_001407658.1:c.3769C>T NP_001394587.1:p.His1257Tyr missense NM_001407659.1:c.3766C>T NP_001394588.1:p.His1256Tyr missense NM_001407660.1:c.3766C>T NP_001394589.1:p.His1256Tyr missense NM_001407661.1:c.3766C>T NP_001394590.1:p.His1256Tyr missense NM_001407662.1:c.3766C>T NP_001394591.1:p.His1256Tyr missense NM_001407663.1:c.3769C>T NP_001394592.1:p.His1257Tyr missense NM_001407664.1:c.3724C>T NP_001394593.1:p.His1242Tyr missense NM_001407665.1:c.3724C>T NP_001394594.1:p.His1242Tyr missense NM_001407666.1:c.3724C>T NP_001394595.1:p.His1242Tyr missense NM_001407667.1:c.3724C>T NP_001394596.1:p.His1242Tyr missense NM_001407668.1:c.3724C>T NP_001394597.1:p.His1242Tyr missense NM_001407669.1:c.3724C>T NP_001394598.1:p.His1242Tyr missense NM_001407670.1:c.3721C>T NP_001394599.1:p.His1241Tyr missense NM_001407671.1:c.3721C>T NP_001394600.1:p.His1241Tyr missense NM_001407672.1:c.3721C>T NP_001394601.1:p.His1241Tyr missense NM_001407673.1:c.3721C>T NP_001394602.1:p.His1241Tyr missense NM_001407674.1:c.3724C>T NP_001394603.1:p.His1242Tyr missense NM_001407675.1:c.3724C>T NP_001394604.1:p.His1242Tyr missense NM_001407676.1:c.3724C>T NP_001394605.1:p.His1242Tyr missense NM_001407677.1:c.3724C>T NP_001394606.1:p.His1242Tyr missense NM_001407678.1:c.3724C>T NP_001394607.1:p.His1242Tyr missense NM_001407679.1:c.3724C>T NP_001394608.1:p.His1242Tyr missense NM_001407680.1:c.3724C>T NP_001394609.1:p.His1242Tyr missense NM_001407681.1:c.3724C>T NP_001394610.1:p.His1242Tyr missense NM_001407682.1:c.3724C>T NP_001394611.1:p.His1242Tyr missense NM_001407683.1:c.3724C>T NP_001394612.1:p.His1242Tyr missense NM_001407684.1:c.3847C>T NP_001394613.1:p.His1283Tyr missense NM_001407685.1:c.3721C>T NP_001394614.1:p.His1241Tyr missense NM_001407686.1:c.3721C>T NP_001394615.1:p.His1241Tyr missense NM_001407687.1:c.3721C>T NP_001394616.1:p.His1241Tyr missense NM_001407688.1:c.3721C>T NP_001394617.1:p.His1241Tyr missense NM_001407689.1:c.3721C>T NP_001394618.1:p.His1241Tyr missense NM_001407690.1:c.3721C>T NP_001394619.1:p.His1241Tyr missense NM_001407691.1:c.3721C>T NP_001394620.1:p.His1241Tyr missense NM_001407692.1:c.3706C>T NP_001394621.1:p.His1236Tyr missense NM_001407694.1:c.3706C>T NP_001394623.1:p.His1236Tyr missense NM_001407695.1:c.3706C>T NP_001394624.1:p.His1236Tyr missense NM_001407696.1:c.3706C>T NP_001394625.1:p.His1236Tyr missense NM_001407697.1:c.3706C>T NP_001394626.1:p.His1236Tyr missense NM_001407698.1:c.3706C>T NP_001394627.1:p.His1236Tyr missense NM_001407724.1:c.3706C>T NP_001394653.1:p.His1236Tyr missense NM_001407725.1:c.3706C>T NP_001394654.1:p.His1236Tyr missense NM_001407726.1:c.3706C>T NP_001394655.1:p.His1236Tyr missense NM_001407727.1:c.3706C>T NP_001394656.1:p.His1236Tyr missense NM_001407728.1:c.3706C>T NP_001394657.1:p.His1236Tyr missense NM_001407729.1:c.3706C>T NP_001394658.1:p.His1236Tyr missense NM_001407730.1:c.3706C>T NP_001394659.1:p.His1236Tyr missense NM_001407731.1:c.3706C>T NP_001394660.1:p.His1236Tyr missense NM_001407732.1:c.3706C>T NP_001394661.1:p.His1236Tyr missense NM_001407733.1:c.3706C>T NP_001394662.1:p.His1236Tyr missense NM_001407734.1:c.3706C>T NP_001394663.1:p.His1236Tyr missense NM_001407735.1:c.3706C>T NP_001394664.1:p.His1236Tyr missense NM_001407736.1:c.3706C>T NP_001394665.1:p.His1236Tyr missense NM_001407737.1:c.3706C>T NP_001394666.1:p.His1236Tyr missense NM_001407738.1:c.3706C>T NP_001394667.1:p.His1236Tyr missense NM_001407739.1:c.3706C>T NP_001394668.1:p.His1236Tyr missense NM_001407740.1:c.3703C>T NP_001394669.1:p.His1235Tyr missense NM_001407741.1:c.3703C>T NP_001394670.1:p.His1235Tyr missense NM_001407742.1:c.3703C>T NP_001394671.1:p.His1235Tyr missense NM_001407743.1:c.3703C>T NP_001394672.1:p.His1235Tyr missense NM_001407744.1:c.3703C>T NP_001394673.1:p.His1235Tyr missense NM_001407745.1:c.3703C>T NP_001394674.1:p.His1235Tyr missense NM_001407746.1:c.3703C>T NP_001394675.1:p.His1235Tyr missense NM_001407747.1:c.3703C>T NP_001394676.1:p.His1235Tyr missense NM_001407748.1:c.3703C>T NP_001394677.1:p.His1235Tyr missense NM_001407749.1:c.3703C>T NP_001394678.1:p.His1235Tyr missense NM_001407750.1:c.3706C>T NP_001394679.1:p.His1236Tyr missense NM_001407751.1:c.3706C>T NP_001394680.1:p.His1236Tyr missense NM_001407752.1:c.3706C>T NP_001394681.1:p.His1236Tyr missense NM_001407838.1:c.3703C>T NP_001394767.1:p.His1235Tyr missense NM_001407839.1:c.3703C>T NP_001394768.1:p.His1235Tyr missense NM_001407841.1:c.3703C>T NP_001394770.1:p.His1235Tyr missense NM_001407842.1:c.3703C>T NP_001394771.1:p.His1235Tyr missense NM_001407843.1:c.3703C>T NP_001394772.1:p.His1235Tyr missense NM_001407844.1:c.3703C>T NP_001394773.1:p.His1235Tyr missense NM_001407845.1:c.3703C>T NP_001394774.1:p.His1235Tyr missense NM_001407846.1:c.3703C>T NP_001394775.1:p.His1235Tyr missense NM_001407847.1:c.3703C>T NP_001394776.1:p.His1235Tyr missense NM_001407848.1:c.3703C>T NP_001394777.1:p.His1235Tyr missense NM_001407849.1:c.3703C>T NP_001394778.1:p.His1235Tyr missense NM_001407850.1:c.3706C>T NP_001394779.1:p.His1236Tyr missense NM_001407851.1:c.3706C>T NP_001394780.1:p.His1236Tyr missense NM_001407852.1:c.3706C>T NP_001394781.1:p.His1236Tyr missense NM_001407853.1:c.3634C>T NP_001394782.1:p.His1212Tyr missense NM_001407854.1:c.3847C>T NP_001394783.1:p.His1283Tyr missense NM_001407858.1:c.3847C>T NP_001394787.1:p.His1283Tyr missense NM_001407859.1:c.3847C>T NP_001394788.1:p.His1283Tyr missense NM_001407860.1:c.3844C>T NP_001394789.1:p.His1282Tyr missense NM_001407861.1:c.3844C>T NP_001394790.1:p.His1282Tyr missense NM_001407862.1:c.3646C>T NP_001394791.1:p.His1216Tyr missense NM_001407863.1:c.3724C>T NP_001394792.1:p.His1242Tyr missense NM_001407874.1:c.3643C>T NP_001394803.1:p.His1215Tyr missense NM_001407875.1:c.3643C>T NP_001394804.1:p.His1215Tyr missense NM_001407879.1:c.3637C>T NP_001394808.1:p.His1213Tyr missense NM_001407881.1:c.3637C>T NP_001394810.1:p.His1213Tyr missense NM_001407882.1:c.3637C>T NP_001394811.1:p.His1213Tyr missense NM_001407884.1:c.3637C>T NP_001394813.1:p.His1213Tyr missense NM_001407885.1:c.3637C>T NP_001394814.1:p.His1213Tyr missense NM_001407886.1:c.3637C>T NP_001394815.1:p.His1213Tyr missense NM_001407887.1:c.3637C>T NP_001394816.1:p.His1213Tyr missense NM_001407889.1:c.3637C>T NP_001394818.1:p.His1213Tyr missense NM_001407894.1:c.3634C>T NP_001394823.1:p.His1212Tyr missense NM_001407895.1:c.3634C>T NP_001394824.1:p.His1212Tyr missense NM_001407896.1:c.3634C>T NP_001394825.1:p.His1212Tyr missense NM_001407897.1:c.3634C>T NP_001394826.1:p.His1212Tyr missense NM_001407898.1:c.3634C>T NP_001394827.1:p.His1212Tyr missense NM_001407899.1:c.3634C>T NP_001394828.1:p.His1212Tyr missense NM_001407900.1:c.3637C>T NP_001394829.1:p.His1213Tyr missense NM_001407902.1:c.3637C>T NP_001394831.1:p.His1213Tyr missense NM_001407904.1:c.3637C>T NP_001394833.1:p.His1213Tyr missense NM_001407906.1:c.3637C>T NP_001394835.1:p.His1213Tyr missense NM_001407907.1:c.3637C>T NP_001394836.1:p.His1213Tyr missense NM_001407908.1:c.3637C>T NP_001394837.1:p.His1213Tyr missense NM_001407909.1:c.3637C>T NP_001394838.1:p.His1213Tyr missense NM_001407910.1:c.3637C>T NP_001394839.1:p.His1213Tyr missense NM_001407915.1:c.3634C>T NP_001394844.1:p.His1212Tyr missense NM_001407916.1:c.3634C>T NP_001394845.1:p.His1212Tyr missense NM_001407917.1:c.3634C>T NP_001394846.1:p.His1212Tyr missense NM_001407918.1:c.3634C>T NP_001394847.1:p.His1212Tyr missense NM_001407919.1:c.3724C>T NP_001394848.1:p.His1242Tyr missense NM_001407920.1:c.3583C>T NP_001394849.1:p.His1195Tyr missense NM_001407921.1:c.3583C>T NP_001394850.1:p.His1195Tyr missense NM_001407922.1:c.3583C>T NP_001394851.1:p.His1195Tyr missense NM_001407923.1:c.3583C>T NP_001394852.1:p.His1195Tyr missense NM_001407924.1:c.3583C>T NP_001394853.1:p.His1195Tyr missense NM_001407925.1:c.3583C>T NP_001394854.1:p.His1195Tyr missense NM_001407926.1:c.3583C>T NP_001394855.1:p.His1195Tyr missense NM_001407927.1:c.3583C>T NP_001394856.1:p.His1195Tyr missense NM_001407928.1:c.3583C>T NP_001394857.1:p.His1195Tyr missense NM_001407929.1:c.3583C>T NP_001394858.1:p.His1195Tyr missense NM_001407930.1:c.3580C>T NP_001394859.1:p.His1194Tyr missense NM_001407931.1:c.3580C>T NP_001394860.1:p.His1194Tyr missense NM_001407932.1:c.3580C>T NP_001394861.1:p.His1194Tyr missense NM_001407933.1:c.3583C>T NP_001394862.1:p.His1195Tyr missense NM_001407934.1:c.3580C>T NP_001394863.1:p.His1194Tyr missense NM_001407935.1:c.3583C>T NP_001394864.1:p.His1195Tyr missense NM_001407936.1:c.3580C>T NP_001394865.1:p.His1194Tyr missense NM_001407937.1:c.3724C>T NP_001394866.1:p.His1242Tyr missense NM_001407938.1:c.3724C>T NP_001394867.1:p.His1242Tyr missense NM_001407939.1:c.3724C>T NP_001394868.1:p.His1242Tyr missense NM_001407940.1:c.3721C>T NP_001394869.1:p.His1241Tyr missense NM_001407941.1:c.3721C>T NP_001394870.1:p.His1241Tyr missense NM_001407942.1:c.3706C>T NP_001394871.1:p.His1236Tyr missense NM_001407943.1:c.3703C>T NP_001394872.1:p.His1235Tyr missense NM_001407944.1:c.3706C>T NP_001394873.1:p.His1236Tyr missense NM_001407945.1:c.3706C>T NP_001394874.1:p.His1236Tyr missense NM_001407946.1:c.3514C>T NP_001394875.1:p.His1172Tyr missense NM_001407947.1:c.3514C>T NP_001394876.1:p.His1172Tyr missense NM_001407948.1:c.3514C>T NP_001394877.1:p.His1172Tyr missense NM_001407949.1:c.3514C>T NP_001394878.1:p.His1172Tyr missense NM_001407950.1:c.3514C>T NP_001394879.1:p.His1172Tyr missense NM_001407951.1:c.3514C>T NP_001394880.1:p.His1172Tyr missense NM_001407952.1:c.3514C>T NP_001394881.1:p.His1172Tyr missense NM_001407953.1:c.3514C>T NP_001394882.1:p.His1172Tyr missense NM_001407954.1:c.3511C>T NP_001394883.1:p.His1171Tyr missense NM_001407955.1:c.3511C>T NP_001394884.1:p.His1171Tyr missense NM_001407956.1:c.3511C>T NP_001394885.1:p.His1171Tyr missense NM_001407957.1:c.3514C>T NP_001394886.1:p.His1172Tyr missense NM_001407958.1:c.3511C>T NP_001394887.1:p.His1171Tyr missense NM_001407959.1:c.3466C>T NP_001394888.1:p.His1156Tyr missense NM_001407960.1:c.3466C>T NP_001394889.1:p.His1156Tyr missense NM_001407962.1:c.3463C>T NP_001394891.1:p.His1155Tyr missense NM_001407963.1:c.3466C>T NP_001394892.1:p.His1156Tyr missense NM_001407964.1:c.3703C>T NP_001394893.1:p.His1235Tyr missense NM_001407965.1:c.3343C>T NP_001394894.1:p.His1115Tyr missense NM_001407966.1:c.2959C>T NP_001394895.1:p.His987Tyr missense NM_001407967.1:c.2959C>T NP_001394896.1:p.His987Tyr missense NM_001407968.1:c.1243C>T NP_001394897.1:p.His415Tyr missense NM_001407969.1:c.1243C>T NP_001394898.1:p.His415Tyr missense NM_001407970.1:c.788-652C>T intron variant NM_001407971.1:c.788-652C>T intron variant NM_001407972.1:c.785-652C>T intron variant NM_001407973.1:c.788-652C>T intron variant NM_001407974.1:c.788-652C>T intron variant NM_001407975.1:c.788-652C>T intron variant NM_001407976.1:c.788-652C>T intron variant NM_001407977.1:c.788-652C>T intron variant NM_001407978.1:c.788-652C>T intron variant NM_001407979.1:c.788-652C>T intron variant NM_001407980.1:c.788-652C>T intron variant NM_001407981.1:c.788-652C>T intron variant NM_001407982.1:c.788-652C>T intron variant NM_001407983.1:c.788-652C>T intron variant NM_001407984.1:c.785-652C>T intron variant NM_001407985.1:c.785-652C>T intron variant NM_001407986.1:c.785-652C>T intron variant NM_001407990.1:c.788-652C>T intron variant NM_001407991.1:c.785-652C>T intron variant NM_001407992.1:c.785-652C>T intron variant NM_001407993.1:c.788-652C>T intron variant NM_001408392.1:c.785-652C>T intron variant NM_001408396.1:c.785-652C>T intron variant NM_001408397.1:c.785-652C>T intron variant NM_001408398.1:c.785-652C>T intron variant NM_001408399.1:c.785-652C>T intron variant NM_001408400.1:c.785-652C>T intron variant NM_001408401.1:c.785-652C>T intron variant NM_001408402.1:c.785-652C>T intron variant NM_001408403.1:c.788-652C>T intron variant NM_001408404.1:c.788-652C>T intron variant NM_001408406.1:c.791-661C>T intron variant NM_001408407.1:c.785-652C>T intron variant NM_001408408.1:c.779-652C>T intron variant NM_001408409.1:c.710-652C>T intron variant NM_001408410.1:c.647-652C>T intron variant NM_001408411.1:c.710-652C>T intron variant NM_001408412.1:c.710-652C>T intron variant NM_001408413.1:c.707-652C>T intron variant NM_001408414.1:c.710-652C>T intron variant NM_001408415.1:c.710-652C>T intron variant NM_001408416.1:c.707-652C>T intron variant NM_001408418.1:c.671-652C>T intron variant NM_001408419.1:c.671-652C>T intron variant NM_001408420.1:c.671-652C>T intron variant NM_001408421.1:c.668-652C>T intron variant NM_001408422.1:c.671-652C>T intron variant NM_001408423.1:c.671-652C>T intron variant NM_001408424.1:c.668-652C>T intron variant NM_001408425.1:c.665-652C>T intron variant NM_001408426.1:c.665-652C>T intron variant NM_001408427.1:c.665-652C>T intron variant NM_001408428.1:c.665-652C>T intron variant NM_001408429.1:c.665-652C>T intron variant NM_001408430.1:c.665-652C>T intron variant NM_001408431.1:c.668-652C>T intron variant NM_001408432.1:c.662-652C>T intron variant NM_001408433.1:c.662-652C>T intron variant NM_001408434.1:c.662-652C>T intron variant NM_001408435.1:c.662-652C>T intron variant NM_001408436.1:c.665-652C>T intron variant NM_001408437.1:c.665-652C>T intron variant NM_001408438.1:c.665-652C>T intron variant NM_001408439.1:c.665-652C>T intron variant NM_001408440.1:c.665-652C>T intron variant NM_001408441.1:c.665-652C>T intron variant NM_001408442.1:c.665-652C>T intron variant NM_001408443.1:c.665-652C>T intron variant NM_001408444.1:c.665-652C>T intron variant NM_001408445.1:c.662-652C>T intron variant NM_001408446.1:c.662-652C>T intron variant NM_001408447.1:c.662-652C>T intron variant NM_001408448.1:c.662-652C>T intron variant NM_001408450.1:c.662-652C>T intron variant NM_001408451.1:c.653-652C>T intron variant NM_001408452.1:c.647-652C>T intron variant NM_001408453.1:c.647-652C>T intron variant NM_001408454.1:c.647-652C>T intron variant NM_001408455.1:c.647-652C>T intron variant NM_001408456.1:c.647-652C>T intron variant NM_001408457.1:c.647-652C>T intron variant NM_001408458.1:c.647-652C>T intron variant NM_001408459.1:c.647-652C>T intron variant NM_001408460.1:c.647-652C>T intron variant NM_001408461.1:c.647-652C>T intron variant NM_001408462.1:c.644-652C>T intron variant NM_001408463.1:c.644-652C>T intron variant NM_001408464.1:c.644-652C>T intron variant NM_001408465.1:c.644-652C>T intron variant NM_001408466.1:c.647-652C>T intron variant NM_001408467.1:c.647-652C>T intron variant NM_001408468.1:c.644-652C>T intron variant NM_001408469.1:c.647-652C>T intron variant NM_001408470.1:c.644-652C>T intron variant NM_001408472.1:c.788-652C>T intron variant NM_001408473.1:c.785-652C>T intron variant NM_001408474.1:c.587-652C>T intron variant NM_001408475.1:c.584-652C>T intron variant NM_001408476.1:c.587-652C>T intron variant NM_001408478.1:c.578-652C>T intron variant NM_001408479.1:c.578-652C>T intron variant NM_001408480.1:c.578-652C>T intron variant NM_001408481.1:c.578-652C>T intron variant NM_001408482.1:c.578-652C>T intron variant NM_001408483.1:c.578-652C>T intron variant NM_001408484.1:c.578-652C>T intron variant NM_001408485.1:c.578-652C>T intron variant NM_001408489.1:c.578-652C>T intron variant NM_001408490.1:c.575-652C>T intron variant NM_001408491.1:c.575-652C>T intron variant NM_001408492.1:c.578-652C>T intron variant NM_001408493.1:c.575-652C>T intron variant NM_001408494.1:c.548-652C>T intron variant NM_001408495.1:c.545-652C>T intron variant NM_001408496.1:c.524-652C>T intron variant NM_001408497.1:c.524-652C>T intron variant NM_001408498.1:c.524-652C>T intron variant NM_001408499.1:c.524-652C>T intron variant NM_001408500.1:c.524-652C>T intron variant NM_001408501.1:c.524-652C>T intron variant NM_001408502.1:c.455-652C>T intron variant NM_001408503.1:c.521-652C>T intron variant NM_001408504.1:c.521-652C>T intron variant NM_001408505.1:c.521-652C>T intron variant NM_001408506.1:c.461-652C>T intron variant NM_001408507.1:c.461-652C>T intron variant NM_001408508.1:c.452-652C>T intron variant NM_001408509.1:c.452-652C>T intron variant NM_001408510.1:c.407-652C>T intron variant NM_001408511.1:c.404-652C>T intron variant NM_001408512.1:c.284-652C>T intron variant NM_001408513.1:c.578-652C>T intron variant NM_001408514.1:c.578-652C>T intron variant NM_007297.4:c.3706C>T NP_009228.2:p.His1236Tyr missense NM_007298.4:c.788-652C>T intron variant NM_007299.4:c.788-652C>T intron variant NM_007300.4:c.3847C>T NP_009231.2:p.His1283Tyr missense NR_027676.1:n.3983C>T NC_000017.11:g.43091684G>A NC_000017.10:g.41243701G>A NG_005905.2:g.126300C>T NG_087068.1:g.666G>A LRG_292:g.126300C>T LRG_292t1:c.3847C>T LRG_292p1:p.His1283Tyr - Protein change
- H1283Y, H1236Y, H1155Y, H1212Y, H1256Y, H987Y, H1156Y, H1171Y, H1194Y, H1195Y, H1215Y, H1241Y, H1257Y, H1282Y, H415Y, H1115Y, H1172Y, H1213Y, H1280Y, H1216Y, H1235Y, H1242Y
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091683:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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 |
13041 | 14847 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Mar 23, 2023 | RCV000509805.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003851235.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
|
Uncertain significance
(Oct 13, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000608093.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The p.H1283Y variant (also known as c.3847C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide … (more)
The p.H1283Y variant (also known as c.3847C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3847. The histidine at codon 1283 is replaced by tyrosine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.H1283Y remains unclear. (less)
|
Comment:
Comment:
The p.H1283Y variant (also known as c.3847C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3847. The histidine at codon 1283 is replaced by tyrosine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.H1283Y remains unclear.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
The p.H1283Y variant (also known as c.3847C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 3847. The histidine at codon 1283 is replaced by tyrosine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.H1283Y remains unclear.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Text-mined citations for rs1555586946 ...
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 May 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.