rs140233356
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_032043.3(BRIP1):c.2830C>T(p.Gln944*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_032043.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135824
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Familial cancer of breast Pathogenic:2
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This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. -
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Pathogenic:1
This sequence change creates a premature translational stop signal (p.Gln944*) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). This variant is present in population databases (rs140233356, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 487435). For these reasons, this variant has been classified as Pathogenic. -
Ovarian neoplasm;C1836860:Fanconi anemia complementation group J Pathogenic:1
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Hereditary cancer-predisposing syndrome Pathogenic:1
The p.Q944* pathogenic mutation (also known as c.2830C>T), located in coding exon 18 of the BRIP1 gene, results from a C to T substitution at nucleotide position 2830. This changes the amino acid from a glutamine to a stop codon within coding exon 18. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at