chr17-61693442-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_032043.3(BRIP1):c.2563C>A(p.Arg855Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R855C) has been classified as Uncertain significance.
Frequency
Consequence
NM_032043.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2563C>A | p.Arg855Ser | missense_variant | 18/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2563C>A | p.Arg855Ser | missense_variant | 18/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460784Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726760
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2021 | This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 821489). 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 855 of the BRIP1 protein (p.Arg855Ser). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and serine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2019 | The p.R855S variant (also known as c.2563C>A), located in coding exon 17 of the BRIP1 gene, results from a C to A substitution at nucleotide position 2563. The arginine at codon 855 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at