rs761401027
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032043.3(BRIP1):āc.610T>Gā(p.Ser204Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_032043.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.610T>G | p.Ser204Ala | missense_variant | 6/20 | ENST00000259008.7 | NP_114432.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.610T>G | p.Ser204Ala | missense_variant | 6/20 | 1 | NM_032043.3 | ENSP00000259008 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251328Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135838
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461524Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727084
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 | Labcorp Genetics (formerly Invitae), Labcorp | Mar 20, 2023 | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 233008). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (rs761401027, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 204 of the BRIP1 protein (p.Ser204Ala). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2023 | The p.S204A variant (also known as c.610T>G), located in coding exon 5 of the BRIP1 gene, results from a T to G substitution at nucleotide position 610. The serine at codon 204 is replaced by alanine, an amino acid with similar properties. This amino acid position is 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. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at