rs545107676
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBS1BS2_Supporting
The NM_000465.4(BARD1):c.44G>T(p.Arg15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,587,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000465.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000148 AC: 30AN: 202228Hom.: 0 AF XY: 0.000187 AC XY: 21AN XY: 112216
GnomAD4 exome AF: 0.0000571 AC: 82AN: 1435650Hom.: 0 Cov.: 74 AF XY: 0.0000800 AC XY: 57AN XY: 712644
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152338Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74482
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not specified Benign:1
Variant summary: BARD1 c.44G>T (p.Arg15Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 202228 control chromosomes, predominantly at a frequency of 0.001 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 4-fold the estimated maximal expected allele frequency for a pathogenic variant in BARD1 causing Breast Cancer phenotype (0.00025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.44G>T in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. They cited the variant as likely benign (n=2) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. -
Familial cancer of breast Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at