chr17-61784272-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_032043.3(BRIP1):c.1626C>T(p.Ser542Ser) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000151 in 1,611,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_032043.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000331 AC: 83AN: 251124Hom.: 0 AF XY: 0.000501 AC XY: 68AN XY: 135738
GnomAD4 exome AF: 0.000155 AC: 226AN: 1459600Hom.: 0 Cov.: 31 AF XY: 0.000220 AC XY: 160AN XY: 726198
GnomAD4 genome AF: 0.000118 AC: 18AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74440
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:3
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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. -
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not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:2
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Variant summary: The BRIP1 c.1626C>T (p.Ser542Ser) variant involves the alteration of a conserved nucleotide causing a synonymous change, which 3/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts the remove of ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 48/121252 (1/2525) control chromosomes, predominantly observed in the South Asian cohort, 38/16490 (1/434), which is about 37 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant, 1/16000. Therefore, suggesting this is likely a benign polymorphism found primarily in population(s) of South Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign. -
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
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Fanconi anemia complementation group J Benign:1
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Familial cancer of breast Benign:1
This variant is considered likely benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at