rs1555572407
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032043.3(BRIP1):c.3731_*5del variant causes a stop lost, 3 prime UTR change. The variant allele was found at a frequency of 0.000000688 in 1,452,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
BRIP1
NM_032043.3 stop_lost, 3_prime_UTR
NM_032043.3 stop_lost, 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.65
Genes affected
BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.3731_*5del | stop_lost, 3_prime_UTR_variant | 20/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.3731_*5del | stop_lost, 3_prime_UTR_variant | 20/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452444Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 723162
GnomAD4 exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 19, 2023 | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met1244Thrfs*2) in the BRIP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the BRIP1 protein. ClinVar contains an entry for this variant (Variation ID: 461165). 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.3731_*5del25 variant (also known as p.M1244Tfs*2), located between coding exon 19 and the 3'-UTR of the BRIP1 gene, results from a deletion of 25 nucleotides (TGTTTCCTGGTTTTAAGTAATAATA) at positions 3731 to *5 causing a translational frameshift with a predicted alternate stop codon. This alteration occurs at the 3' terminus of the BRIP1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 6 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at