This sequence change replaces alanine with glutamic acid at codon 1453 of the BRCA1 protein (p.Ala1453Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4358C>A (p.Ala1453Glu)
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.
Uncertain significance
2
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.4358C>A (p.Ala1453Glu)
Variation ID: 1479797 Accession: VCV001479797.8
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43076614 (GRCh38) [ NCBI UCSC ] 17: 41228631 (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 Mar 28, 2022 May 1, 2024 Aug 14, 2021 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4358C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1453Glu missense NM_001407571.1:c.4145C>A NP_001394500.1:p.Ala1382Glu missense NM_001407581.1:c.4424C>A NP_001394510.1:p.Ala1475Glu missense NM_001407582.1:c.4424C>A NP_001394511.1:p.Ala1475Glu missense NM_001407583.1:c.4424-3C>A intron variant NM_001407585.1:c.4424-3C>A intron variant NM_001407587.1:c.4421C>A NP_001394516.1:p.Ala1474Glu missense NM_001407590.1:c.4421-3C>A intron variant NM_001407591.1:c.4421-3C>A intron variant NM_001407593.1:c.4358C>A NP_001394522.1:p.Ala1453Glu missense NM_001407594.1:c.4358C>A NP_001394523.1:p.Ala1453Glu missense NM_001407596.1:c.4358C>A NP_001394525.1:p.Ala1453Glu missense NM_001407597.1:c.4358C>A NP_001394526.1:p.Ala1453Glu missense NM_001407598.1:c.4358C>A NP_001394527.1:p.Ala1453Glu missense NM_001407602.1:c.4358C>A NP_001394531.1:p.Ala1453Glu missense NM_001407603.1:c.4358C>A NP_001394532.1:p.Ala1453Glu missense NM_001407605.1:c.4358C>A NP_001394534.1:p.Ala1453Glu missense NM_001407610.1:c.4355C>A NP_001394539.1:p.Ala1452Glu missense NM_001407611.1:c.4355C>A NP_001394540.1:p.Ala1452Glu missense NM_001407612.1:c.4355C>A NP_001394541.1:p.Ala1452Glu missense NM_001407613.1:c.4355C>A NP_001394542.1:p.Ala1452Glu missense NM_001407614.1:c.4355C>A NP_001394543.1:p.Ala1452Glu missense NM_001407615.1:c.4355C>A NP_001394544.1:p.Ala1452Glu missense NM_001407616.1:c.4358-3C>A intron variant NM_001407617.1:c.4358-3C>A intron variant NM_001407618.1:c.4358-3C>A intron variant NM_001407619.1:c.4358-3C>A intron variant NM_001407620.1:c.4358-3C>A intron variant NM_001407621.1:c.4358-3C>A intron variant NM_001407622.1:c.4358-3C>A intron variant NM_001407623.1:c.4358-3C>A intron variant NM_001407624.1:c.4355C>A NP_001394553.1:p.Ala1452Glu missense NM_001407625.1:c.4355C>A NP_001394554.1:p.Ala1452Glu missense NM_001407626.1:c.4355C>A NP_001394555.1:p.Ala1452Glu missense NM_001407627.1:c.4352C>A NP_001394556.1:p.Ala1451Glu missense NM_001407628.1:c.4352C>A NP_001394557.1:p.Ala1451Glu missense NM_001407629.1:c.4352C>A NP_001394558.1:p.Ala1451Glu missense NM_001407630.1:c.4352C>A NP_001394559.1:p.Ala1451Glu missense NM_001407631.1:c.4352C>A NP_001394560.1:p.Ala1451Glu missense NM_001407632.1:c.4352C>A NP_001394561.1:p.Ala1451Glu missense NM_001407633.1:c.4355-3C>A intron variant NM_001407634.1:c.4355-3C>A intron variant NM_001407635.1:c.4355-3C>A intron variant NM_001407636.1:c.4355-3C>A intron variant NM_001407637.1:c.4355-3C>A intron variant NM_001407638.1:c.4355-3C>A intron variant NM_001407639.1:c.4355-3C>A intron variant NM_001407640.1:c.4355-3C>A intron variant NM_001407641.1:c.4355-3C>A intron variant NM_001407642.1:c.4355-3C>A intron variant NM_001407644.1:c.4352-3C>A intron variant NM_001407645.1:c.4352-3C>A intron variant NM_001407646.1:c.4346C>A NP_001394575.1:p.Ala1449Glu missense NM_001407647.1:c.4346-3C>A intron variant NM_001407648.1:c.4301C>A NP_001394577.1:p.Ala1434Glu missense NM_001407649.1:c.4298C>A NP_001394578.1:p.Ala1433Glu missense NM_001407652.1:c.4358C>A NP_001394581.1:p.Ala1453Glu missense NM_001407653.1:c.4280C>A NP_001394582.1:p.Ala1427Glu missense NM_001407654.1:c.4280C>A NP_001394583.1:p.Ala1427Glu missense NM_001407655.1:c.4280C>A NP_001394584.1:p.Ala1427Glu missense NM_001407656.1:c.4277C>A NP_001394585.1:p.Ala1426Glu missense NM_001407657.1:c.4280-3C>A intron variant NM_001407658.1:c.4280-3C>A intron variant NM_001407659.1:c.4274C>A NP_001394588.1:p.Ala1425Glu missense NM_001407660.1:c.4274C>A NP_001394589.1:p.Ala1425Glu missense NM_001407661.1:c.4277-3C>A intron variant NM_001407662.1:c.4277-3C>A intron variant NM_001407663.1:c.4277-3C>A intron variant NM_001407664.1:c.4235C>A NP_001394593.1:p.Ala1412Glu missense NM_001407665.1:c.4235C>A NP_001394594.1:p.Ala1412Glu missense NM_001407666.1:c.4235C>A NP_001394595.1:p.Ala1412Glu missense NM_001407667.1:c.4235C>A NP_001394596.1:p.Ala1412Glu missense NM_001407668.1:c.4235C>A NP_001394597.1:p.Ala1412Glu missense NM_001407669.1:c.4235C>A NP_001394598.1:p.Ala1412Glu missense NM_001407670.1:c.4232C>A NP_001394599.1:p.Ala1411Glu missense NM_001407671.1:c.4232C>A NP_001394600.1:p.Ala1411Glu missense NM_001407672.1:c.4232C>A NP_001394601.1:p.Ala1411Glu missense NM_001407673.1:c.4232C>A NP_001394602.1:p.Ala1411Glu missense NM_001407674.1:c.4232C>A NP_001394603.1:p.Ala1411Glu missense NM_001407675.1:c.4232C>A NP_001394604.1:p.Ala1411Glu missense NM_001407676.1:c.4232C>A NP_001394605.1:p.Ala1411Glu missense NM_001407677.1:c.4235-3C>A intron variant NM_001407678.1:c.4235-3C>A intron variant NM_001407679.1:c.4235-3C>A intron variant NM_001407680.1:c.4235-3C>A intron variant NM_001407681.1:c.4232-3C>A intron variant NM_001407682.1:c.4232-3C>A intron variant NM_001407683.1:c.4232-3C>A intron variant NM_001407684.1:c.4358C>A NP_001394613.1:p.Ala1453Glu missense NM_001407685.1:c.4229C>A NP_001394614.1:p.Ala1410Glu missense NM_001407686.1:c.4229C>A NP_001394615.1:p.Ala1410Glu missense NM_001407687.1:c.4229C>A NP_001394616.1:p.Ala1410Glu missense NM_001407688.1:c.4232-3C>A intron variant NM_001407689.1:c.4232-3C>A intron variant NM_001407690.1:c.4229-3C>A intron variant NM_001407691.1:c.4229-3C>A intron variant NM_001407692.1:c.4217C>A NP_001394621.1:p.Ala1406Glu missense NM_001407694.1:c.4217C>A NP_001394623.1:p.Ala1406Glu missense NM_001407695.1:c.4217C>A NP_001394624.1:p.Ala1406Glu missense NM_001407696.1:c.4217C>A NP_001394625.1:p.Ala1406Glu missense NM_001407697.1:c.4217C>A NP_001394626.1:p.Ala1406Glu missense NM_001407698.1:c.4217C>A NP_001394627.1:p.Ala1406Glu missense NM_001407724.1:c.4217C>A NP_001394653.1:p.Ala1406Glu missense NM_001407725.1:c.4217C>A NP_001394654.1:p.Ala1406Glu missense NM_001407726.1:c.4217C>A NP_001394655.1:p.Ala1406Glu missense NM_001407727.1:c.4217C>A NP_001394656.1:p.Ala1406Glu missense NM_001407728.1:c.4217C>A NP_001394657.1:p.Ala1406Glu missense NM_001407729.1:c.4217C>A NP_001394658.1:p.Ala1406Glu missense NM_001407730.1:c.4217C>A NP_001394659.1:p.Ala1406Glu missense NM_001407731.1:c.4217C>A NP_001394660.1:p.Ala1406Glu missense NM_001407732.1:c.4217-3C>A intron variant NM_001407733.1:c.4217-3C>A intron variant NM_001407734.1:c.4217-3C>A intron variant NM_001407735.1:c.4217-3C>A intron variant NM_001407736.1:c.4217-3C>A intron variant NM_001407737.1:c.4217-3C>A intron variant NM_001407738.1:c.4217-3C>A intron variant NM_001407739.1:c.4217-3C>A intron variant NM_001407740.1:c.4214C>A NP_001394669.1:p.Ala1405Glu missense NM_001407741.1:c.4214C>A NP_001394670.1:p.Ala1405Glu missense NM_001407742.1:c.4214C>A NP_001394671.1:p.Ala1405Glu missense NM_001407743.1:c.4214C>A NP_001394672.1:p.Ala1405Glu missense NM_001407744.1:c.4214C>A NP_001394673.1:p.Ala1405Glu missense NM_001407745.1:c.4214C>A NP_001394674.1:p.Ala1405Glu missense NM_001407746.1:c.4214C>A NP_001394675.1:p.Ala1405Glu missense NM_001407747.1:c.4214C>A NP_001394676.1:p.Ala1405Glu missense NM_001407748.1:c.4214C>A NP_001394677.1:p.Ala1405Glu missense NM_001407749.1:c.4214C>A NP_001394678.1:p.Ala1405Glu missense NM_001407750.1:c.4214C>A NP_001394679.1:p.Ala1405Glu missense NM_001407751.1:c.4214C>A NP_001394680.1:p.Ala1405Glu missense NM_001407752.1:c.4214C>A NP_001394681.1:p.Ala1405Glu missense NM_001407838.1:c.4214-3C>A intron variant NM_001407839.1:c.4214-3C>A intron variant NM_001407841.1:c.4214-3C>A intron variant NM_001407842.1:c.4214-3C>A intron variant NM_001407843.1:c.4214-3C>A intron variant NM_001407844.1:c.4214-3C>A intron variant NM_001407845.1:c.4214-3C>A intron variant NM_001407846.1:c.4214-3C>A intron variant NM_001407847.1:c.4211C>A NP_001394776.1:p.Ala1404Glu missense NM_001407848.1:c.4211C>A NP_001394777.1:p.Ala1404Glu missense NM_001407849.1:c.4211C>A NP_001394778.1:p.Ala1404Glu missense NM_001407850.1:c.4214-3C>A intron variant NM_001407851.1:c.4214-3C>A intron variant NM_001407852.1:c.4214-3C>A intron variant NM_001407853.1:c.4211C>A NP_001394782.1:p.Ala1404Glu missense NM_001407854.1:c.4358C>A NP_001394783.1:p.Ala1453Glu missense NM_001407858.1:c.4358-3C>A intron variant NM_001407859.1:c.4358-3C>A intron variant NM_001407860.1:c.4355C>A NP_001394789.1:p.Ala1452Glu missense NM_001407861.1:c.4355-3C>A intron variant NM_001407862.1:c.4157C>A NP_001394791.1:p.Ala1386Glu missense NM_001407863.1:c.4235-3C>A intron variant NM_001407874.1:c.4154-3C>A intron variant NM_001407875.1:c.4154-3C>A intron variant NM_001407879.1:c.4148C>A NP_001394808.1:p.Ala1383Glu missense NM_001407881.1:c.4148C>A NP_001394810.1:p.Ala1383Glu missense NM_001407882.1:c.4148C>A NP_001394811.1:p.Ala1383Glu missense NM_001407884.1:c.4148C>A NP_001394813.1:p.Ala1383Glu missense NM_001407885.1:c.4148C>A NP_001394814.1:p.Ala1383Glu missense NM_001407886.1:c.4148C>A NP_001394815.1:p.Ala1383Glu missense NM_001407887.1:c.4148C>A NP_001394816.1:p.Ala1383Glu missense NM_001407889.1:c.4148C>A NP_001394818.1:p.Ala1383Glu missense NM_001407894.1:c.4145C>A NP_001394823.1:p.Ala1382Glu missense NM_001407895.1:c.4145C>A NP_001394824.1:p.Ala1382Glu missense NM_001407896.1:c.4145C>A NP_001394825.1:p.Ala1382Glu missense NM_001407897.1:c.4145C>A NP_001394826.1:p.Ala1382Glu missense NM_001407898.1:c.4145C>A NP_001394827.1:p.Ala1382Glu missense NM_001407899.1:c.4145C>A NP_001394828.1:p.Ala1382Glu missense NM_001407900.1:c.4148-3C>A intron variant NM_001407902.1:c.4148-3C>A intron variant NM_001407904.1:c.4148-3C>A intron variant NM_001407906.1:c.4148-3C>A intron variant NM_001407907.1:c.4145C>A NP_001394836.1:p.Ala1382Glu missense NM_001407908.1:c.4145C>A NP_001394837.1:p.Ala1382Glu missense NM_001407909.1:c.4145C>A NP_001394838.1:p.Ala1382Glu missense NM_001407910.1:c.4145C>A NP_001394839.1:p.Ala1382Glu missense NM_001407915.1:c.4142C>A NP_001394844.1:p.Ala1381Glu missense NM_001407916.1:c.4145-3C>A intron variant NM_001407917.1:c.4145-3C>A intron variant NM_001407918.1:c.4145-3C>A intron variant NM_001407919.1:c.4235C>A NP_001394848.1:p.Ala1412Glu missense NM_001407920.1:c.4094C>A NP_001394849.1:p.Ala1365Glu missense NM_001407921.1:c.4094C>A NP_001394850.1:p.Ala1365Glu missense NM_001407922.1:c.4094C>A NP_001394851.1:p.Ala1365Glu missense NM_001407923.1:c.4094C>A NP_001394852.1:p.Ala1365Glu missense NM_001407924.1:c.4094C>A NP_001394853.1:p.Ala1365Glu missense NM_001407925.1:c.4094C>A NP_001394854.1:p.Ala1365Glu missense NM_001407926.1:c.4094C>A NP_001394855.1:p.Ala1365Glu missense NM_001407927.1:c.4094-3C>A intron variant NM_001407928.1:c.4094-3C>A intron variant NM_001407929.1:c.4094-3C>A intron variant NM_001407930.1:c.4091C>A NP_001394859.1:p.Ala1364Glu missense NM_001407931.1:c.4091C>A NP_001394860.1:p.Ala1364Glu missense NM_001407932.1:c.4091C>A NP_001394861.1:p.Ala1364Glu missense NM_001407933.1:c.4091C>A NP_001394862.1:p.Ala1364Glu missense NM_001407934.1:c.4088C>A NP_001394863.1:p.Ala1363Glu missense NM_001407935.1:c.4091-3C>A intron variant NM_001407936.1:c.4091-3C>A intron variant NM_001407937.1:c.4235C>A NP_001394866.1:p.Ala1412Glu missense NM_001407938.1:c.4235C>A NP_001394867.1:p.Ala1412Glu missense NM_001407939.1:c.4235-3C>A intron variant NM_001407940.1:c.4232C>A NP_001394869.1:p.Ala1411Glu missense NM_001407941.1:c.4232-3C>A intron variant NM_001407942.1:c.4217C>A NP_001394871.1:p.Ala1406Glu missense NM_001407943.1:c.4214C>A NP_001394872.1:p.Ala1405Glu missense NM_001407944.1:c.4217-3C>A intron variant NM_001407945.1:c.4217-3C>A intron variant NM_001407946.1:c.4025C>A NP_001394875.1:p.Ala1342Glu missense NM_001407947.1:c.4025C>A NP_001394876.1:p.Ala1342Glu missense NM_001407948.1:c.4025C>A NP_001394877.1:p.Ala1342Glu missense NM_001407949.1:c.4025C>A NP_001394878.1:p.Ala1342Glu missense NM_001407950.1:c.4025-3C>A intron variant NM_001407951.1:c.4025-3C>A intron variant NM_001407952.1:c.4022C>A NP_001394881.1:p.Ala1341Glu missense NM_001407953.1:c.4022C>A NP_001394882.1:p.Ala1341Glu missense NM_001407954.1:c.4022C>A NP_001394883.1:p.Ala1341Glu missense NM_001407955.1:c.4022C>A NP_001394884.1:p.Ala1341Glu missense NM_001407956.1:c.4019C>A NP_001394885.1:p.Ala1340Glu missense NM_001407957.1:c.4022-3C>A intron variant NM_001407958.1:c.4022-3C>A intron variant NM_001407959.1:c.3977C>A NP_001394888.1:p.Ala1326Glu missense NM_001407960.1:c.3977-3C>A intron variant NM_001407962.1:c.3974C>A NP_001394891.1:p.Ala1325Glu missense NM_001407963.1:c.3974-3C>A intron variant NM_001407964.1:c.4214-5376C>A intron variant NM_001407965.1:c.3851C>A NP_001394894.1:p.Ala1284Glu missense NM_001407966.1:c.3470C>A NP_001394895.1:p.Ala1157Glu missense NM_001407967.1:c.3470-3C>A intron variant NM_001407968.1:c.1754C>A NP_001394897.1:p.Ala585Glu missense NM_001407969.1:c.1751C>A NP_001394898.1:p.Ala584Glu missense NM_001407970.1:c.1115C>A NP_001394899.1:p.Ala372Glu missense NM_001407971.1:c.1115C>A NP_001394900.1:p.Ala372Glu missense NM_001407972.1:c.1112C>A NP_001394901.1:p.Ala371Glu missense NM_001407973.1:c.1049C>A NP_001394902.1:p.Ala350Glu missense NM_001407974.1:c.1049C>A NP_001394903.1:p.Ala350Glu missense NM_001407975.1:c.1049C>A NP_001394904.1:p.Ala350Glu missense NM_001407976.1:c.1049C>A NP_001394905.1:p.Ala350Glu missense NM_001407977.1:c.1049C>A NP_001394906.1:p.Ala350Glu missense NM_001407978.1:c.1049C>A NP_001394907.1:p.Ala350Glu missense NM_001407979.1:c.1046C>A NP_001394908.1:p.Ala349Glu missense NM_001407980.1:c.1046C>A NP_001394909.1:p.Ala349Glu missense NM_001407981.1:c.1046C>A NP_001394910.1:p.Ala349Glu missense NM_001407982.1:c.1046C>A NP_001394911.1:p.Ala349Glu missense NM_001407983.1:c.1046C>A NP_001394912.1:p.Ala349Glu missense NM_001407984.1:c.1046C>A NP_001394913.1:p.Ala349Glu missense NM_001407985.1:c.1046C>A NP_001394914.1:p.Ala349Glu missense NM_001407986.1:c.1046C>A NP_001394915.1:p.Ala349Glu missense NM_001407990.1:c.1046C>A NP_001394919.1:p.Ala349Glu missense NM_001407991.1:c.1046C>A NP_001394920.1:p.Ala349Glu missense NM_001407992.1:c.1046C>A NP_001394921.1:p.Ala349Glu missense NM_001407993.1:c.1049-3C>A intron variant NM_001408392.1:c.1046-3C>A intron variant NM_001408396.1:c.1046-3C>A intron variant NM_001408397.1:c.1046-3C>A intron variant NM_001408398.1:c.1046-3C>A intron variant NM_001408399.1:c.1046-3C>A intron variant NM_001408400.1:c.1043C>A NP_001395329.1:p.Ala348Glu missense NM_001408401.1:c.1043C>A NP_001395330.1:p.Ala348Glu missense NM_001408402.1:c.1043C>A NP_001395331.1:p.Ala348Glu missense NM_001408403.1:c.1046-3C>A intron variant NM_001408404.1:c.1046-3C>A intron variant NM_001408406.1:c.1040C>A NP_001395335.1:p.Ala347Glu missense NM_001408407.1:c.1043-3C>A intron variant NM_001408408.1:c.1040C>A NP_001395337.1:p.Ala347Glu missense NM_001408409.1:c.1037C>A NP_001395338.1:p.Ala346Glu missense NM_001408410.1:c.974C>A NP_001395339.1:p.Ala325Glu missense NM_001408411.1:c.971C>A NP_001395340.1:p.Ala324Glu missense NM_001408412.1:c.971-3C>A intron variant NM_001408413.1:c.968C>A NP_001395342.1:p.Ala323Glu missense NM_001408414.1:c.971-3C>A intron variant NM_001408415.1:c.971-3C>A intron variant NM_001408416.1:c.968C>A NP_001395345.1:p.Ala323Glu missense NM_001408418.1:c.932C>A NP_001395347.1:p.Ala311Glu missense NM_001408419.1:c.932C>A NP_001395348.1:p.Ala311Glu missense NM_001408420.1:c.932C>A NP_001395349.1:p.Ala311Glu missense NM_001408421.1:c.929C>A NP_001395350.1:p.Ala310Glu missense NM_001408422.1:c.932-3C>A intron variant NM_001408423.1:c.932-3C>A intron variant NM_001408424.1:c.929C>A NP_001395353.1:p.Ala310Glu missense NM_001408425.1:c.926C>A NP_001395354.1:p.Ala309Glu missense NM_001408426.1:c.926C>A NP_001395355.1:p.Ala309Glu missense NM_001408427.1:c.926C>A NP_001395356.1:p.Ala309Glu missense NM_001408428.1:c.926C>A NP_001395357.1:p.Ala309Glu missense NM_001408429.1:c.926C>A NP_001395358.1:p.Ala309Glu missense NM_001408430.1:c.926C>A NP_001395359.1:p.Ala309Glu missense NM_001408431.1:c.929-3C>A intron variant NM_001408432.1:c.923C>A NP_001395361.1:p.Ala308Glu missense NM_001408433.1:c.923C>A NP_001395362.1:p.Ala308Glu missense NM_001408434.1:c.923C>A NP_001395363.1:p.Ala308Glu missense NM_001408435.1:c.923C>A NP_001395364.1:p.Ala308Glu missense NM_001408436.1:c.926-3C>A intron variant NM_001408437.1:c.926-3C>A intron variant NM_001408438.1:c.926-3C>A intron variant NM_001408439.1:c.926-3C>A intron variant NM_001408440.1:c.926-3C>A intron variant NM_001408441.1:c.923C>A NP_001395370.1:p.Ala308Glu missense NM_001408442.1:c.923C>A NP_001395371.1:p.Ala308Glu missense NM_001408443.1:c.923C>A NP_001395372.1:p.Ala308Glu missense NM_001408444.1:c.923C>A NP_001395373.1:p.Ala308Glu missense NM_001408445.1:c.923-3C>A intron variant NM_001408446.1:c.923-3C>A intron variant NM_001408447.1:c.923-3C>A intron variant NM_001408448.1:c.923-3C>A intron variant NM_001408450.1:c.923-3C>A intron variant NM_001408451.1:c.914C>A NP_001395380.1:p.Ala305Glu missense NM_001408452.1:c.908C>A NP_001395381.1:p.Ala303Glu missense NM_001408453.1:c.908C>A NP_001395382.1:p.Ala303Glu missense NM_001408454.1:c.908C>A NP_001395383.1:p.Ala303Glu missense NM_001408455.1:c.908C>A NP_001395384.1:p.Ala303Glu missense NM_001408456.1:c.908C>A NP_001395385.1:p.Ala303Glu missense NM_001408457.1:c.908C>A NP_001395386.1:p.Ala303Glu missense NM_001408458.1:c.908-3C>A intron variant NM_001408459.1:c.908-3C>A intron variant NM_001408460.1:c.908-3C>A intron variant NM_001408461.1:c.908-3C>A intron variant NM_001408462.1:c.905C>A NP_001395391.1:p.Ala302Glu missense NM_001408463.1:c.905C>A NP_001395392.1:p.Ala302Glu missense NM_001408464.1:c.905C>A NP_001395393.1:p.Ala302Glu missense NM_001408465.1:c.905C>A NP_001395394.1:p.Ala302Glu missense NM_001408466.1:c.905C>A NP_001395395.1:p.Ala302Glu missense NM_001408467.1:c.905C>A NP_001395396.1:p.Ala302Glu missense NM_001408468.1:c.905-3C>A intron variant NM_001408469.1:c.905-3C>A intron variant NM_001408470.1:c.902C>A NP_001395399.1:p.Ala301Glu missense NM_001408472.1:c.1046C>A NP_001395401.1:p.Ala349Glu missense NM_001408473.1:c.1046-3C>A intron variant NM_001408474.1:c.848C>A NP_001395403.1:p.Ala283Glu missense NM_001408475.1:c.845C>A NP_001395404.1:p.Ala282Glu missense NM_001408476.1:c.848-3C>A intron variant NM_001408478.1:c.839C>A NP_001395407.1:p.Ala280Glu missense NM_001408479.1:c.839C>A NP_001395408.1:p.Ala280Glu missense NM_001408480.1:c.839C>A NP_001395409.1:p.Ala280Glu missense NM_001408481.1:c.839-3C>A intron variant NM_001408482.1:c.839-3C>A intron variant NM_001408483.1:c.839-3C>A intron variant NM_001408484.1:c.839-3C>A intron variant NM_001408485.1:c.839-3C>A intron variant NM_001408489.1:c.836C>A NP_001395418.1:p.Ala279Glu missense NM_001408490.1:c.836C>A NP_001395419.1:p.Ala279Glu missense NM_001408491.1:c.836C>A NP_001395420.1:p.Ala279Glu missense NM_001408492.1:c.836-3C>A intron variant NM_001408493.1:c.836-3C>A intron variant NM_001408494.1:c.809C>A NP_001395423.1:p.Ala270Glu missense NM_001408495.1:c.806-3C>A intron variant NM_001408496.1:c.785C>A NP_001395425.1:p.Ala262Glu missense NM_001408497.1:c.785C>A NP_001395426.1:p.Ala262Glu missense NM_001408498.1:c.785C>A NP_001395427.1:p.Ala262Glu missense NM_001408499.1:c.785C>A NP_001395428.1:p.Ala262Glu missense NM_001408500.1:c.785C>A NP_001395429.1:p.Ala262Glu missense NM_001408501.1:c.785C>A NP_001395430.1:p.Ala262Glu missense NM_001408502.1:c.782C>A NP_001395431.1:p.Ala261Glu missense NM_001408503.1:c.782C>A NP_001395432.1:p.Ala261Glu missense NM_001408504.1:c.782C>A NP_001395433.1:p.Ala261Glu missense NM_001408505.1:c.782-3C>A intron variant NM_001408506.1:c.722C>A NP_001395435.1:p.Ala241Glu missense NM_001408507.1:c.719C>A NP_001395436.1:p.Ala240Glu missense NM_001408508.1:c.710C>A NP_001395437.1:p.Ala237Glu missense NM_001408509.1:c.710-3C>A intron variant NM_001408510.1:c.668C>A NP_001395439.1:p.Ala223Glu missense NM_001408511.1:c.665C>A NP_001395440.1:p.Ala222Glu missense NM_001408512.1:c.545C>A NP_001395441.1:p.Ala182Glu missense NM_001408513.1:c.836-5376C>A intron variant NM_001408514.1:c.838+5790C>A intron variant NM_007297.4:c.4217C>A NP_009228.2:p.Ala1406Glu missense NM_007298.4:c.1049-3C>A intron variant NM_007299.4:c.1049-3C>A intron variant NM_007300.4:c.4424-3C>A intron variant NR_027676.1:n.4494C>A NC_000017.11:g.43076614G>T NC_000017.10:g.41228631G>T NG_005905.2:g.141370C>A LRG_292:g.141370C>A LRG_292t1:c.4358C>A LRG_292p1:p.Ala1453Glu - Protein change
- A1406E, A1157E, A1325E, A1382E, A1404E, A1405E, A1411E, A1425E, A1434E, A1449E, A270E, A279E, A309E, A347E, A350E, A371E, A1340E, A1342E, A1365E, A1386E, A1427E, A1433E, A1451E, A237E, A240E, A280E, A305E, A346E, A348E, A349E, A585E, A1284E, A1326E, A1341E, A1383E, A1452E, A1475E, A182E, A241E, A283E, A301E, A303E, A308E, A310E, A311E, A324E, A325E, A372E, A584E, A1363E, A1364E, A1381E, A1410E, A1412E, A1426E, A1474E, A222E, A223E, A261E, A262E, A282E, A302E, A323E, A1453E
- Other names
- -
- Canonical SPDI
- NC_000017.11:43076613:G:T
-
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 |
13073 | 14882 | |
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) |
criteria provided, single submitter
|
Aug 14, 2021 | RCV001976922.6 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 13, 2017 | RCV002331561.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002261225.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces alanine with glutamic acid at codon 1453 of the BRCA1 protein (p.Ala1453Glu). The alanine residue is moderately conserved and there is … (more)
This sequence change replaces alanine with glutamic acid at codon 1453 of the BRCA1 protein (p.Ala1453Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(Nov 13, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002633117.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.A1453E variant (also known as c.4358C>A) is located in coding exon 12 of the BRCA1 gene. The alanine at codon 1453 is replaced by … (more)
The p.A1453E variant (also known as c.4358C>A) is located in coding exon 12 of the BRCA1 gene. The alanine at codon 1453 is replaced by glutamic acid, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 12. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.A1453E variant (also known as c.4358C>A) is located in coding exon 12 of the BRCA1 gene. The alanine at codon 1453 is replaced by glutamic acid, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 12. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration 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:
This sequence change replaces alanine with glutamic acid at codon 1453 of the BRCA1 protein (p.Ala1453Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The p.A1453E variant (also known as c.4358C>A) is located in coding exon 12 of the BRCA1 gene. The alanine at codon 1453 is replaced by glutamic acid, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 12. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1171055085 ...
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 Sep 29, 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.