rs945661395
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_032043.3(BRIP1):c.1514C>T(p.Ser505Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.1514C>T | p.Ser505Leu | missense_variant | 11/20 | ENST00000259008.7 | NP_114432.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.1514C>T | p.Ser505Leu | missense_variant | 11/20 | 1 | NM_032043.3 | ENSP00000259008 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251374Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135856
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
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 | May 21, 2023 | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. 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: 407805). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 505 of the BRIP1 protein (p.Ser505Leu). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2023 | The p.S505L variant (also known as c.1514C>T), located in coding exon 10 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1514. The serine at codon 505 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at