The p.F1571S variant (also known as c.4712T>C), located in coding exon 14 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4712. The phenylalanine at codon 1571 is replaced by serine, an amino acid with highly dissimilar properties. This variant had 50.88% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is well 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 this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4712T>C (p.Phe1571Ser)
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.
(7)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
7
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4712T>C (p.Phe1571Ser)
Variation ID: 55268 Accession: VCV000055268.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43071202 (GRCh38) [ NCBI UCSC ] 17: 41223219 (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 Apr 1, 2014 May 1, 2024 Jan 27, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4712T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Phe1571Ser missense NM_001407571.1:c.4499T>C NP_001394500.1:p.Phe1500Ser missense NM_001407581.1:c.4778T>C NP_001394510.1:p.Phe1593Ser missense NM_001407582.1:c.4778T>C NP_001394511.1:p.Phe1593Ser missense NM_001407583.1:c.4775T>C NP_001394512.1:p.Phe1592Ser missense NM_001407585.1:c.4775T>C NP_001394514.1:p.Phe1592Ser missense NM_001407587.1:c.4775T>C NP_001394516.1:p.Phe1592Ser missense NM_001407590.1:c.4772T>C NP_001394519.1:p.Phe1591Ser missense NM_001407591.1:c.4772T>C NP_001394520.1:p.Phe1591Ser missense NM_001407593.1:c.4712T>C NP_001394522.1:p.Phe1571Ser missense NM_001407594.1:c.4712T>C NP_001394523.1:p.Phe1571Ser missense NM_001407596.1:c.4712T>C NP_001394525.1:p.Phe1571Ser missense NM_001407597.1:c.4712T>C NP_001394526.1:p.Phe1571Ser missense NM_001407598.1:c.4712T>C NP_001394527.1:p.Phe1571Ser missense NM_001407602.1:c.4712T>C NP_001394531.1:p.Phe1571Ser missense NM_001407603.1:c.4712T>C NP_001394532.1:p.Phe1571Ser missense NM_001407605.1:c.4712T>C NP_001394534.1:p.Phe1571Ser missense NM_001407610.1:c.4709T>C NP_001394539.1:p.Phe1570Ser missense NM_001407611.1:c.4709T>C NP_001394540.1:p.Phe1570Ser missense NM_001407612.1:c.4709T>C NP_001394541.1:p.Phe1570Ser missense NM_001407613.1:c.4709T>C NP_001394542.1:p.Phe1570Ser missense NM_001407614.1:c.4709T>C NP_001394543.1:p.Phe1570Ser missense NM_001407615.1:c.4709T>C NP_001394544.1:p.Phe1570Ser missense NM_001407616.1:c.4709T>C NP_001394545.1:p.Phe1570Ser missense NM_001407617.1:c.4709T>C NP_001394546.1:p.Phe1570Ser missense NM_001407618.1:c.4709T>C NP_001394547.1:p.Phe1570Ser missense NM_001407619.1:c.4709T>C NP_001394548.1:p.Phe1570Ser missense NM_001407620.1:c.4709T>C NP_001394549.1:p.Phe1570Ser missense NM_001407621.1:c.4709T>C NP_001394550.1:p.Phe1570Ser missense NM_001407622.1:c.4709T>C NP_001394551.1:p.Phe1570Ser missense NM_001407623.1:c.4709T>C NP_001394552.1:p.Phe1570Ser missense NM_001407624.1:c.4709T>C NP_001394553.1:p.Phe1570Ser missense NM_001407625.1:c.4709T>C NP_001394554.1:p.Phe1570Ser missense NM_001407626.1:c.4709T>C NP_001394555.1:p.Phe1570Ser missense NM_001407627.1:c.4706T>C NP_001394556.1:p.Phe1569Ser missense NM_001407628.1:c.4706T>C NP_001394557.1:p.Phe1569Ser missense NM_001407629.1:c.4706T>C NP_001394558.1:p.Phe1569Ser missense NM_001407630.1:c.4706T>C NP_001394559.1:p.Phe1569Ser missense NM_001407631.1:c.4706T>C NP_001394560.1:p.Phe1569Ser missense NM_001407632.1:c.4706T>C NP_001394561.1:p.Phe1569Ser missense NM_001407633.1:c.4706T>C NP_001394562.1:p.Phe1569Ser missense NM_001407634.1:c.4706T>C NP_001394563.1:p.Phe1569Ser missense NM_001407635.1:c.4706T>C NP_001394564.1:p.Phe1569Ser missense NM_001407636.1:c.4706T>C NP_001394565.1:p.Phe1569Ser missense NM_001407637.1:c.4706T>C NP_001394566.1:p.Phe1569Ser missense NM_001407638.1:c.4706T>C NP_001394567.1:p.Phe1569Ser missense NM_001407639.1:c.4706T>C NP_001394568.1:p.Phe1569Ser missense NM_001407640.1:c.4706T>C NP_001394569.1:p.Phe1569Ser missense NM_001407641.1:c.4706T>C NP_001394570.1:p.Phe1569Ser missense NM_001407642.1:c.4706T>C NP_001394571.1:p.Phe1569Ser missense NM_001407644.1:c.4703T>C NP_001394573.1:p.Phe1568Ser missense NM_001407645.1:c.4703T>C NP_001394574.1:p.Phe1568Ser missense NM_001407646.1:c.4700T>C NP_001394575.1:p.Phe1567Ser missense NM_001407647.1:c.4697T>C NP_001394576.1:p.Phe1566Ser missense NM_001407648.1:c.4655T>C NP_001394577.1:p.Phe1552Ser missense NM_001407649.1:c.4652T>C NP_001394578.1:p.Phe1551Ser missense NM_001407652.1:c.4712T>C NP_001394581.1:p.Phe1571Ser missense NM_001407653.1:c.4634T>C NP_001394582.1:p.Phe1545Ser missense NM_001407654.1:c.4634T>C NP_001394583.1:p.Phe1545Ser missense NM_001407655.1:c.4634T>C NP_001394584.1:p.Phe1545Ser missense NM_001407656.1:c.4631T>C NP_001394585.1:p.Phe1544Ser missense NM_001407657.1:c.4631T>C NP_001394586.1:p.Phe1544Ser missense NM_001407658.1:c.4631T>C NP_001394587.1:p.Phe1544Ser missense NM_001407659.1:c.4628T>C NP_001394588.1:p.Phe1543Ser missense NM_001407660.1:c.4628T>C NP_001394589.1:p.Phe1543Ser missense NM_001407661.1:c.4628T>C NP_001394590.1:p.Phe1543Ser missense NM_001407662.1:c.4628T>C NP_001394591.1:p.Phe1543Ser missense NM_001407663.1:c.4628T>C NP_001394592.1:p.Phe1543Ser missense NM_001407664.1:c.4589T>C NP_001394593.1:p.Phe1530Ser missense NM_001407665.1:c.4589T>C NP_001394594.1:p.Phe1530Ser missense NM_001407666.1:c.4589T>C NP_001394595.1:p.Phe1530Ser missense NM_001407667.1:c.4589T>C NP_001394596.1:p.Phe1530Ser missense NM_001407668.1:c.4589T>C NP_001394597.1:p.Phe1530Ser missense NM_001407669.1:c.4589T>C NP_001394598.1:p.Phe1530Ser missense NM_001407670.1:c.4586T>C NP_001394599.1:p.Phe1529Ser missense NM_001407671.1:c.4586T>C NP_001394600.1:p.Phe1529Ser missense NM_001407672.1:c.4586T>C NP_001394601.1:p.Phe1529Ser missense NM_001407673.1:c.4586T>C NP_001394602.1:p.Phe1529Ser missense NM_001407674.1:c.4586T>C NP_001394603.1:p.Phe1529Ser missense NM_001407675.1:c.4586T>C NP_001394604.1:p.Phe1529Ser missense NM_001407676.1:c.4586T>C NP_001394605.1:p.Phe1529Ser missense NM_001407677.1:c.4586T>C NP_001394606.1:p.Phe1529Ser missense NM_001407678.1:c.4586T>C NP_001394607.1:p.Phe1529Ser missense NM_001407679.1:c.4586T>C NP_001394608.1:p.Phe1529Ser missense NM_001407680.1:c.4586T>C NP_001394609.1:p.Phe1529Ser missense NM_001407681.1:c.4583T>C NP_001394610.1:p.Phe1528Ser missense NM_001407682.1:c.4583T>C NP_001394611.1:p.Phe1528Ser missense NM_001407683.1:c.4583T>C NP_001394612.1:p.Phe1528Ser missense NM_001407684.1:c.4712T>C NP_001394613.1:p.Phe1571Ser missense NM_001407685.1:c.4583T>C NP_001394614.1:p.Phe1528Ser missense NM_001407686.1:c.4583T>C NP_001394615.1:p.Phe1528Ser missense NM_001407687.1:c.4583T>C NP_001394616.1:p.Phe1528Ser missense NM_001407688.1:c.4583T>C NP_001394617.1:p.Phe1528Ser missense NM_001407689.1:c.4583T>C NP_001394618.1:p.Phe1528Ser missense NM_001407690.1:c.4580T>C NP_001394619.1:p.Phe1527Ser missense NM_001407691.1:c.4580T>C NP_001394620.1:p.Phe1527Ser missense NM_001407692.1:c.4571T>C NP_001394621.1:p.Phe1524Ser missense NM_001407694.1:c.4571T>C NP_001394623.1:p.Phe1524Ser missense NM_001407695.1:c.4571T>C NP_001394624.1:p.Phe1524Ser missense NM_001407696.1:c.4571T>C NP_001394625.1:p.Phe1524Ser missense NM_001407697.1:c.4571T>C NP_001394626.1:p.Phe1524Ser missense NM_001407698.1:c.4571T>C NP_001394627.1:p.Phe1524Ser missense NM_001407724.1:c.4571T>C NP_001394653.1:p.Phe1524Ser missense NM_001407725.1:c.4571T>C NP_001394654.1:p.Phe1524Ser missense NM_001407726.1:c.4571T>C NP_001394655.1:p.Phe1524Ser missense NM_001407727.1:c.4571T>C NP_001394656.1:p.Phe1524Ser missense NM_001407728.1:c.4571T>C NP_001394657.1:p.Phe1524Ser missense NM_001407729.1:c.4571T>C NP_001394658.1:p.Phe1524Ser missense NM_001407730.1:c.4571T>C NP_001394659.1:p.Phe1524Ser missense NM_001407731.1:c.4571T>C NP_001394660.1:p.Phe1524Ser missense NM_001407732.1:c.4568T>C NP_001394661.1:p.Phe1523Ser missense NM_001407733.1:c.4568T>C NP_001394662.1:p.Phe1523Ser missense NM_001407734.1:c.4568T>C NP_001394663.1:p.Phe1523Ser missense NM_001407735.1:c.4568T>C NP_001394664.1:p.Phe1523Ser missense NM_001407736.1:c.4568T>C NP_001394665.1:p.Phe1523Ser missense NM_001407737.1:c.4568T>C NP_001394666.1:p.Phe1523Ser missense NM_001407738.1:c.4568T>C NP_001394667.1:p.Phe1523Ser missense NM_001407739.1:c.4568T>C NP_001394668.1:p.Phe1523Ser missense NM_001407740.1:c.4568T>C NP_001394669.1:p.Phe1523Ser missense NM_001407741.1:c.4568T>C NP_001394670.1:p.Phe1523Ser missense NM_001407742.1:c.4568T>C NP_001394671.1:p.Phe1523Ser missense NM_001407743.1:c.4568T>C NP_001394672.1:p.Phe1523Ser missense NM_001407744.1:c.4568T>C NP_001394673.1:p.Phe1523Ser missense NM_001407745.1:c.4568T>C NP_001394674.1:p.Phe1523Ser missense NM_001407746.1:c.4568T>C NP_001394675.1:p.Phe1523Ser missense NM_001407747.1:c.4568T>C NP_001394676.1:p.Phe1523Ser missense NM_001407748.1:c.4568T>C NP_001394677.1:p.Phe1523Ser missense NM_001407749.1:c.4568T>C NP_001394678.1:p.Phe1523Ser missense NM_001407750.1:c.4568T>C NP_001394679.1:p.Phe1523Ser missense NM_001407751.1:c.4568T>C NP_001394680.1:p.Phe1523Ser missense NM_001407752.1:c.4568T>C NP_001394681.1:p.Phe1523Ser missense NM_001407838.1:c.4565T>C NP_001394767.1:p.Phe1522Ser missense NM_001407839.1:c.4565T>C NP_001394768.1:p.Phe1522Ser missense NM_001407841.1:c.4565T>C NP_001394770.1:p.Phe1522Ser missense NM_001407842.1:c.4565T>C NP_001394771.1:p.Phe1522Ser missense NM_001407843.1:c.4565T>C NP_001394772.1:p.Phe1522Ser missense NM_001407844.1:c.4565T>C NP_001394773.1:p.Phe1522Ser missense NM_001407845.1:c.4565T>C NP_001394774.1:p.Phe1522Ser missense NM_001407846.1:c.4565T>C NP_001394775.1:p.Phe1522Ser missense NM_001407847.1:c.4565T>C NP_001394776.1:p.Phe1522Ser missense NM_001407848.1:c.4565T>C NP_001394777.1:p.Phe1522Ser missense NM_001407849.1:c.4565T>C NP_001394778.1:p.Phe1522Ser missense NM_001407850.1:c.4565T>C NP_001394779.1:p.Phe1522Ser missense NM_001407851.1:c.4565T>C NP_001394780.1:p.Phe1522Ser missense NM_001407852.1:c.4565T>C NP_001394781.1:p.Phe1522Ser missense NM_001407853.1:c.4565T>C NP_001394782.1:p.Phe1522Ser missense NM_001407854.1:c.4712T>C NP_001394783.1:p.Phe1571Ser missense NM_001407858.1:c.4709T>C NP_001394787.1:p.Phe1570Ser missense NM_001407859.1:c.4709T>C NP_001394788.1:p.Phe1570Ser missense NM_001407860.1:c.4709T>C NP_001394789.1:p.Phe1570Ser missense NM_001407861.1:c.4706T>C NP_001394790.1:p.Phe1569Ser missense NM_001407862.1:c.4511T>C NP_001394791.1:p.Phe1504Ser missense NM_001407863.1:c.4586T>C NP_001394792.1:p.Phe1529Ser missense NM_001407874.1:c.4505T>C NP_001394803.1:p.Phe1502Ser missense NM_001407875.1:c.4505T>C NP_001394804.1:p.Phe1502Ser missense NM_001407879.1:c.4502T>C NP_001394808.1:p.Phe1501Ser missense NM_001407881.1:c.4502T>C NP_001394810.1:p.Phe1501Ser missense NM_001407882.1:c.4502T>C NP_001394811.1:p.Phe1501Ser missense NM_001407884.1:c.4502T>C NP_001394813.1:p.Phe1501Ser missense NM_001407885.1:c.4502T>C NP_001394814.1:p.Phe1501Ser missense NM_001407886.1:c.4502T>C NP_001394815.1:p.Phe1501Ser missense NM_001407887.1:c.4502T>C NP_001394816.1:p.Phe1501Ser missense NM_001407889.1:c.4502T>C NP_001394818.1:p.Phe1501Ser missense NM_001407894.1:c.4499T>C NP_001394823.1:p.Phe1500Ser missense NM_001407895.1:c.4499T>C NP_001394824.1:p.Phe1500Ser missense NM_001407896.1:c.4499T>C NP_001394825.1:p.Phe1500Ser missense NM_001407897.1:c.4499T>C NP_001394826.1:p.Phe1500Ser missense NM_001407898.1:c.4499T>C NP_001394827.1:p.Phe1500Ser missense NM_001407899.1:c.4499T>C NP_001394828.1:p.Phe1500Ser missense NM_001407900.1:c.4499T>C NP_001394829.1:p.Phe1500Ser missense NM_001407902.1:c.4499T>C NP_001394831.1:p.Phe1500Ser missense NM_001407904.1:c.4499T>C NP_001394833.1:p.Phe1500Ser missense NM_001407906.1:c.4499T>C NP_001394835.1:p.Phe1500Ser missense NM_001407907.1:c.4499T>C NP_001394836.1:p.Phe1500Ser missense NM_001407908.1:c.4499T>C NP_001394837.1:p.Phe1500Ser missense NM_001407909.1:c.4499T>C NP_001394838.1:p.Phe1500Ser missense NM_001407910.1:c.4499T>C NP_001394839.1:p.Phe1500Ser missense NM_001407915.1:c.4496T>C NP_001394844.1:p.Phe1499Ser missense NM_001407916.1:c.4496T>C NP_001394845.1:p.Phe1499Ser missense NM_001407917.1:c.4496T>C NP_001394846.1:p.Phe1499Ser missense NM_001407918.1:c.4496T>C NP_001394847.1:p.Phe1499Ser missense NM_001407919.1:c.4589T>C NP_001394848.1:p.Phe1530Ser missense NM_001407920.1:c.4448T>C NP_001394849.1:p.Phe1483Ser missense NM_001407921.1:c.4448T>C NP_001394850.1:p.Phe1483Ser missense NM_001407922.1:c.4448T>C NP_001394851.1:p.Phe1483Ser missense NM_001407923.1:c.4448T>C NP_001394852.1:p.Phe1483Ser missense NM_001407924.1:c.4448T>C NP_001394853.1:p.Phe1483Ser missense NM_001407925.1:c.4448T>C NP_001394854.1:p.Phe1483Ser missense NM_001407926.1:c.4448T>C NP_001394855.1:p.Phe1483Ser missense NM_001407927.1:c.4445T>C NP_001394856.1:p.Phe1482Ser missense NM_001407928.1:c.4445T>C NP_001394857.1:p.Phe1482Ser missense NM_001407929.1:c.4445T>C NP_001394858.1:p.Phe1482Ser missense NM_001407930.1:c.4445T>C NP_001394859.1:p.Phe1482Ser missense NM_001407931.1:c.4445T>C NP_001394860.1:p.Phe1482Ser missense NM_001407932.1:c.4445T>C NP_001394861.1:p.Phe1482Ser missense NM_001407933.1:c.4445T>C NP_001394862.1:p.Phe1482Ser missense NM_001407934.1:c.4442T>C NP_001394863.1:p.Phe1481Ser missense NM_001407935.1:c.4442T>C NP_001394864.1:p.Phe1481Ser missense NM_001407936.1:c.4442T>C NP_001394865.1:p.Phe1481Ser missense NM_001407937.1:c.4589T>C NP_001394866.1:p.Phe1530Ser missense NM_001407938.1:c.4589T>C NP_001394867.1:p.Phe1530Ser missense NM_001407939.1:c.4586T>C NP_001394868.1:p.Phe1529Ser missense NM_001407940.1:c.4586T>C NP_001394869.1:p.Phe1529Ser missense NM_001407941.1:c.4583T>C NP_001394870.1:p.Phe1528Ser missense NM_001407942.1:c.4571T>C NP_001394871.1:p.Phe1524Ser missense NM_001407943.1:c.4568T>C NP_001394872.1:p.Phe1523Ser missense NM_001407944.1:c.4568T>C NP_001394873.1:p.Phe1523Ser missense NM_001407945.1:c.4568T>C NP_001394874.1:p.Phe1523Ser missense NM_001407946.1:c.4379T>C NP_001394875.1:p.Phe1460Ser missense NM_001407947.1:c.4379T>C NP_001394876.1:p.Phe1460Ser missense NM_001407948.1:c.4379T>C NP_001394877.1:p.Phe1460Ser missense NM_001407949.1:c.4379T>C NP_001394878.1:p.Phe1460Ser missense NM_001407950.1:c.4376T>C NP_001394879.1:p.Phe1459Ser missense NM_001407951.1:c.4376T>C NP_001394880.1:p.Phe1459Ser missense NM_001407952.1:c.4376T>C NP_001394881.1:p.Phe1459Ser missense NM_001407953.1:c.4376T>C NP_001394882.1:p.Phe1459Ser missense NM_001407954.1:c.4376T>C NP_001394883.1:p.Phe1459Ser missense NM_001407955.1:c.4376T>C NP_001394884.1:p.Phe1459Ser missense NM_001407956.1:c.4373T>C NP_001394885.1:p.Phe1458Ser missense NM_001407957.1:c.4373T>C NP_001394886.1:p.Phe1458Ser missense NM_001407958.1:c.4373T>C NP_001394887.1:p.Phe1458Ser missense NM_001407959.1:c.4331T>C NP_001394888.1:p.Phe1444Ser missense NM_001407960.1:c.4328T>C NP_001394889.1:p.Phe1443Ser missense NM_001407962.1:c.4328T>C NP_001394891.1:p.Phe1443Ser missense NM_001407963.1:c.4325T>C NP_001394892.1:p.Phe1442Ser missense NM_001407964.1:c.4250T>C NP_001394893.1:p.Phe1417Ser missense NM_001407965.1:c.4205T>C NP_001394894.1:p.Phe1402Ser missense NM_001407966.1:c.3824T>C NP_001394895.1:p.Phe1275Ser missense NM_001407967.1:c.3821T>C NP_001394896.1:p.Phe1274Ser missense NM_001407968.1:c.2108T>C NP_001394897.1:p.Phe703Ser missense NM_001407969.1:c.2105T>C NP_001394898.1:p.Phe702Ser missense NM_001407970.1:c.1469T>C NP_001394899.1:p.Phe490Ser missense NM_001407971.1:c.1469T>C NP_001394900.1:p.Phe490Ser missense NM_001407972.1:c.1466T>C NP_001394901.1:p.Phe489Ser missense NM_001407973.1:c.1403T>C NP_001394902.1:p.Phe468Ser missense NM_001407974.1:c.1403T>C NP_001394903.1:p.Phe468Ser missense NM_001407975.1:c.1403T>C NP_001394904.1:p.Phe468Ser missense NM_001407976.1:c.1403T>C NP_001394905.1:p.Phe468Ser missense NM_001407977.1:c.1403T>C NP_001394906.1:p.Phe468Ser missense NM_001407978.1:c.1403T>C NP_001394907.1:p.Phe468Ser missense NM_001407979.1:c.1400T>C NP_001394908.1:p.Phe467Ser missense NM_001407980.1:c.1400T>C NP_001394909.1:p.Phe467Ser missense NM_001407981.1:c.1400T>C NP_001394910.1:p.Phe467Ser missense NM_001407982.1:c.1400T>C NP_001394911.1:p.Phe467Ser missense NM_001407983.1:c.1400T>C NP_001394912.1:p.Phe467Ser missense NM_001407984.1:c.1400T>C NP_001394913.1:p.Phe467Ser missense NM_001407985.1:c.1400T>C NP_001394914.1:p.Phe467Ser missense NM_001407986.1:c.1400T>C NP_001394915.1:p.Phe467Ser missense NM_001407990.1:c.1400T>C NP_001394919.1:p.Phe467Ser missense NM_001407991.1:c.1400T>C NP_001394920.1:p.Phe467Ser missense NM_001407992.1:c.1400T>C NP_001394921.1:p.Phe467Ser missense NM_001407993.1:c.1400T>C NP_001394922.1:p.Phe467Ser missense NM_001408392.1:c.1397T>C NP_001395321.1:p.Phe466Ser missense NM_001408396.1:c.1397T>C NP_001395325.1:p.Phe466Ser missense NM_001408397.1:c.1397T>C NP_001395326.1:p.Phe466Ser missense NM_001408398.1:c.1397T>C NP_001395327.1:p.Phe466Ser missense NM_001408399.1:c.1397T>C NP_001395328.1:p.Phe466Ser missense NM_001408400.1:c.1397T>C NP_001395329.1:p.Phe466Ser missense NM_001408401.1:c.1397T>C NP_001395330.1:p.Phe466Ser missense NM_001408402.1:c.1397T>C NP_001395331.1:p.Phe466Ser missense NM_001408403.1:c.1397T>C NP_001395332.1:p.Phe466Ser missense NM_001408404.1:c.1397T>C NP_001395333.1:p.Phe466Ser missense NM_001408406.1:c.1394T>C NP_001395335.1:p.Phe465Ser missense NM_001408407.1:c.1394T>C NP_001395336.1:p.Phe465Ser missense NM_001408408.1:c.1394T>C NP_001395337.1:p.Phe465Ser missense NM_001408409.1:c.1391T>C NP_001395338.1:p.Phe464Ser missense NM_001408410.1:c.1328T>C NP_001395339.1:p.Phe443Ser missense NM_001408411.1:c.1325T>C NP_001395340.1:p.Phe442Ser missense NM_001408412.1:c.1322T>C NP_001395341.1:p.Phe441Ser missense NM_001408413.1:c.1322T>C NP_001395342.1:p.Phe441Ser missense NM_001408414.1:c.1322T>C NP_001395343.1:p.Phe441Ser missense NM_001408415.1:c.1322T>C NP_001395344.1:p.Phe441Ser missense NM_001408416.1:c.1322T>C NP_001395345.1:p.Phe441Ser missense NM_001408418.1:c.1286T>C NP_001395347.1:p.Phe429Ser missense NM_001408419.1:c.1286T>C NP_001395348.1:p.Phe429Ser missense NM_001408420.1:c.1286T>C NP_001395349.1:p.Phe429Ser missense NM_001408421.1:c.1283T>C NP_001395350.1:p.Phe428Ser missense NM_001408422.1:c.1283T>C NP_001395351.1:p.Phe428Ser missense NM_001408423.1:c.1283T>C NP_001395352.1:p.Phe428Ser missense NM_001408424.1:c.1283T>C NP_001395353.1:p.Phe428Ser missense NM_001408425.1:c.1280T>C NP_001395354.1:p.Phe427Ser missense NM_001408426.1:c.1280T>C NP_001395355.1:p.Phe427Ser missense NM_001408427.1:c.1280T>C NP_001395356.1:p.Phe427Ser missense NM_001408428.1:c.1280T>C NP_001395357.1:p.Phe427Ser missense NM_001408429.1:c.1280T>C NP_001395358.1:p.Phe427Ser missense NM_001408430.1:c.1280T>C NP_001395359.1:p.Phe427Ser missense NM_001408431.1:c.1280T>C NP_001395360.1:p.Phe427Ser missense NM_001408432.1:c.1277T>C NP_001395361.1:p.Phe426Ser missense NM_001408433.1:c.1277T>C NP_001395362.1:p.Phe426Ser missense NM_001408434.1:c.1277T>C NP_001395363.1:p.Phe426Ser missense NM_001408435.1:c.1277T>C NP_001395364.1:p.Phe426Ser missense NM_001408436.1:c.1277T>C NP_001395365.1:p.Phe426Ser missense NM_001408437.1:c.1277T>C NP_001395366.1:p.Phe426Ser missense NM_001408438.1:c.1277T>C NP_001395367.1:p.Phe426Ser missense NM_001408439.1:c.1277T>C NP_001395368.1:p.Phe426Ser missense NM_001408440.1:c.1277T>C NP_001395369.1:p.Phe426Ser missense NM_001408441.1:c.1277T>C NP_001395370.1:p.Phe426Ser missense NM_001408442.1:c.1277T>C NP_001395371.1:p.Phe426Ser missense NM_001408443.1:c.1277T>C NP_001395372.1:p.Phe426Ser missense NM_001408444.1:c.1277T>C NP_001395373.1:p.Phe426Ser missense NM_001408445.1:c.1274T>C NP_001395374.1:p.Phe425Ser missense NM_001408446.1:c.1274T>C NP_001395375.1:p.Phe425Ser missense NM_001408447.1:c.1274T>C NP_001395376.1:p.Phe425Ser missense NM_001408448.1:c.1274T>C NP_001395377.1:p.Phe425Ser missense NM_001408450.1:c.1274T>C NP_001395379.1:p.Phe425Ser missense NM_001408451.1:c.1268T>C NP_001395380.1:p.Phe423Ser missense NM_001408452.1:c.1262T>C NP_001395381.1:p.Phe421Ser missense NM_001408453.1:c.1262T>C NP_001395382.1:p.Phe421Ser missense NM_001408454.1:c.1262T>C NP_001395383.1:p.Phe421Ser missense NM_001408455.1:c.1262T>C NP_001395384.1:p.Phe421Ser missense NM_001408456.1:c.1262T>C NP_001395385.1:p.Phe421Ser missense NM_001408457.1:c.1262T>C NP_001395386.1:p.Phe421Ser missense NM_001408458.1:c.1259T>C NP_001395387.1:p.Phe420Ser missense NM_001408459.1:c.1259T>C NP_001395388.1:p.Phe420Ser missense NM_001408460.1:c.1259T>C NP_001395389.1:p.Phe420Ser missense NM_001408461.1:c.1259T>C NP_001395390.1:p.Phe420Ser missense NM_001408462.1:c.1259T>C NP_001395391.1:p.Phe420Ser missense NM_001408463.1:c.1259T>C NP_001395392.1:p.Phe420Ser missense NM_001408464.1:c.1259T>C NP_001395393.1:p.Phe420Ser missense NM_001408465.1:c.1259T>C NP_001395394.1:p.Phe420Ser missense NM_001408466.1:c.1259T>C NP_001395395.1:p.Phe420Ser missense NM_001408467.1:c.1259T>C NP_001395396.1:p.Phe420Ser missense NM_001408468.1:c.1256T>C NP_001395397.1:p.Phe419Ser missense NM_001408469.1:c.1256T>C NP_001395398.1:p.Phe419Ser missense NM_001408470.1:c.1256T>C NP_001395399.1:p.Phe419Ser missense NM_001408472.1:c.1400T>C NP_001395401.1:p.Phe467Ser missense NM_001408473.1:c.1397T>C NP_001395402.1:p.Phe466Ser missense NM_001408474.1:c.1202T>C NP_001395403.1:p.Phe401Ser missense NM_001408475.1:c.1199T>C NP_001395404.1:p.Phe400Ser missense NM_001408476.1:c.1199T>C NP_001395405.1:p.Phe400Ser missense NM_001408478.1:c.1193T>C NP_001395407.1:p.Phe398Ser missense NM_001408479.1:c.1193T>C NP_001395408.1:p.Phe398Ser missense NM_001408480.1:c.1193T>C NP_001395409.1:p.Phe398Ser missense NM_001408481.1:c.1190T>C NP_001395410.1:p.Phe397Ser missense NM_001408482.1:c.1190T>C NP_001395411.1:p.Phe397Ser missense NM_001408483.1:c.1190T>C NP_001395412.1:p.Phe397Ser missense NM_001408484.1:c.1190T>C NP_001395413.1:p.Phe397Ser missense NM_001408485.1:c.1190T>C NP_001395414.1:p.Phe397Ser missense NM_001408489.1:c.1190T>C NP_001395418.1:p.Phe397Ser missense NM_001408490.1:c.1190T>C NP_001395419.1:p.Phe397Ser missense NM_001408491.1:c.1190T>C NP_001395420.1:p.Phe397Ser missense NM_001408492.1:c.1187T>C NP_001395421.1:p.Phe396Ser missense NM_001408493.1:c.1187T>C NP_001395422.1:p.Phe396Ser missense NM_001408494.1:c.1163T>C NP_001395423.1:p.Phe388Ser missense NM_001408495.1:c.1157T>C NP_001395424.1:p.Phe386Ser missense NM_001408496.1:c.1139T>C NP_001395425.1:p.Phe380Ser missense NM_001408497.1:c.1139T>C NP_001395426.1:p.Phe380Ser missense NM_001408498.1:c.1139T>C NP_001395427.1:p.Phe380Ser missense NM_001408499.1:c.1139T>C NP_001395428.1:p.Phe380Ser missense NM_001408500.1:c.1139T>C NP_001395429.1:p.Phe380Ser missense NM_001408501.1:c.1139T>C NP_001395430.1:p.Phe380Ser missense NM_001408502.1:c.1136T>C NP_001395431.1:p.Phe379Ser missense NM_001408503.1:c.1136T>C NP_001395432.1:p.Phe379Ser missense NM_001408504.1:c.1136T>C NP_001395433.1:p.Phe379Ser missense NM_001408505.1:c.1133T>C NP_001395434.1:p.Phe378Ser missense NM_001408506.1:c.1076T>C NP_001395435.1:p.Phe359Ser missense NM_001408507.1:c.1073T>C NP_001395436.1:p.Phe358Ser missense NM_001408508.1:c.1064T>C NP_001395437.1:p.Phe355Ser missense NM_001408509.1:c.1061T>C NP_001395438.1:p.Phe354Ser missense NM_001408510.1:c.1022T>C NP_001395439.1:p.Phe341Ser missense NM_001408511.1:c.1019T>C NP_001395440.1:p.Phe340Ser missense NM_001408512.1:c.899T>C NP_001395441.1:p.Phe300Ser missense NM_001408513.1:c.872T>C NP_001395442.1:p.Phe291Ser missense NM_007297.4:c.4571T>C NP_009228.2:p.Phe1524Ser missense NM_007298.4:c.1400T>C NP_009229.2:p.Phe467Ser missense NM_007299.4:c.1400T>C NP_009230.2:p.Phe467Ser missense NM_007300.4:c.4775T>C NP_009231.2:p.Phe1592Ser missense NM_007304.2:c.1400T>C NP_009235.2:p.Phe467Ser missense NR_027676.2:n.4889T>C non-coding transcript variant NC_000017.11:g.43071202A>G NC_000017.10:g.41223219A>G NG_005905.2:g.146782T>C LRG_292:g.146782T>C LRG_292t1:c.4712T>C LRG_292p1:p.Phe1571Ser U14680.1:n.4831T>C - Protein change
- F1571S, F467S, F1524S, F1592S, F1275S, F1458S, F1460S, F1500S, F1530S, F1551S, F1552S, F1570S, F291S, F341S, F355S, F378S, F388S, F421S, F466S, F1417S, F1444S, F1501S, F1566S, F300S, F358S, F379S, F380S, F396S, F398S, F420S, F427S, F428S, F489S, F490S, F702S, F703S, F1274S, F1442S, F1481S, F1482S, F1499S, F1502S, F1504S, F1522S, F1529S, F1543S, F1545S, F1568S, F1569S, F1591S, F1593S, F340S, F386S, F397S, F401S, F419S, F423S, F426S, F429S, F442S, F1402S, F1443S, F1459S, F1483S, F1523S, F1527S, F1528S, F1544S, F1567S, F354S, F359S, F400S, F425S, F441S, F443S, F464S, F465S, F468S
- Other names
- -
- Canonical SPDI
- NC_000017.11:43071201:A:G
-
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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
no assertion criteria provided
|
Dec 17, 2010 | RCV000112388.4 | |
| Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 21, 2022 | RCV000759547.8 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 27, 2024 | RCV001022941.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 3, 2023 | RCV001298706.6 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jan 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001184741.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.F1571S variant (also known as c.4712T>C), located in coding exon 14 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.F1571S variant (also known as c.4712T>C), located in coding exon 14 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4712. The phenylalanine at codon 1571 is replaced by serine, an amino acid with highly dissimilar properties. This variant had 50.88% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is well 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 this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jun 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002759047.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
Published functional studies demonstrate transcriptional activity comparable to wild type (Woods 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis … (more)
Published functional studies demonstrate transcriptional activity comparable to wild type (Woods 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 4831T>C; This variant is associated with the following publications: (PMID: 10220405, 11301010, 9974970, 10923033, 28781887) (less)
|
|
|
Uncertain significance
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009435.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
|
Uncertain significance
(Dec 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888928.3
First in ClinVar: Mar 14, 2019 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000004 (1/251268 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more)
The frequency of this variant in the general population, 0.000004 (1/251268 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in a large breast cancer association study in one individual with breast cancer (PMID: 33471991 (2021), https://databases.lovd.nl/shared/variants/BRCA1). Additionally, a functional study yielded inconclusive results regarding the effect of this variant on BRCA1 protein function (PMID: 28781887 (2016)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain significance
(Nov 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001487769.4
First in ClinVar: Mar 07, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1571 of the BRCA1 protein (p.Phe1571Ser). … (more)
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1571 of the BRCA1 protein (p.Phe1571Ser). This variant is present in population databases (rs273901740, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55268). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. 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)
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Uncertain significance
(Mar 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001340173.2
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces phenylalanine with serine at codon 1571 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces phenylalanine with serine at codon 1571 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown this variant results in a moderate decrease in transcriptional activity compared to wild type (PMID: 28781887). In a large breast cancer case-control study, this variant has been observed in 1/60466 cases and 0/53461 controls (PMID: 33471991). This variant has been identified in 1/251268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Dec 17, 2010)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145164.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Geographic origin: Austria
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Comment:
Comment:
Published functional studies demonstrate transcriptional activity comparable to wild type (Woods 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 4831T>C; This variant is associated with the following publications: (PMID: 10220405, 11301010, 9974970, 10923033, 28781887)
Comment:
The frequency of this variant in the general population, 0.000004 (1/251268 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in a large breast cancer association study in one individual with breast cancer (PMID: 33471991 (2021), https://databases.lovd.nl/shared/variants/BRCA1). Additionally, a functional study yielded inconclusive results regarding the effect of this variant on BRCA1 protein function (PMID: 28781887 (2016)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1571 of the BRCA1 protein (p.Phe1571Ser). This variant is present in population databases (rs273901740, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55268). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
This missense variant replaces phenylalanine with serine at codon 1571 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown this variant results in a moderate decrease in transcriptional activity compared to wild type (PMID: 28781887). In a large breast cancer case-control study, this variant has been observed in 1/60466 cases and 0/53461 controls (PMID: 33471991). This variant has been identified in 1/251268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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:
The p.F1571S variant (also known as c.4712T>C), located in coding exon 14 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4712. The phenylalanine at codon 1571 is replaced by serine, an amino acid with highly dissimilar properties. This variant had 50.88% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is well 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 this alteration remains unclear.
Comment:
Published functional studies demonstrate transcriptional activity comparable to wild type (Woods 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 4831T>C; This variant is associated with the following publications: (PMID: 10220405, 11301010, 9974970, 10923033, 28781887)
Comment:
The frequency of this variant in the general population, 0.000004 (1/251268 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in a large breast cancer association study in one individual with breast cancer (PMID: 33471991 (2021), https://databases.lovd.nl/shared/variants/BRCA1). Additionally, a functional study yielded inconclusive results regarding the effect of this variant on BRCA1 protein function (PMID: 28781887 (2016)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1571 of the BRCA1 protein (p.Phe1571Ser). This variant is present in population databases (rs273901740, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 55268). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
This missense variant replaces phenylalanine with serine at codon 1571 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown this variant results in a moderate decrease in transcriptional activity compared to wild type (PMID: 28781887). In a large breast cancer case-control study, this variant has been observed in 1/60466 cases and 0/53461 controls (PMID: 33471991). This variant has been identified in 1/251268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs273901740 ...
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.