rs754280048

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP3

The NM_032043.3(BRIP1):​c.2806G>T​(p.Glu936Ter) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

BRIP1
NM_032043.3 stop_gained

Scores

2
1
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363
Variant links:
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 Likely_pathogenic. Variant got 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.252 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRIP1NM_032043.3 linkuse as main transcriptc.2806G>T p.Glu936Ter stop_gained 19/20 ENST00000259008.7 NP_114432.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRIP1ENST00000259008.7 linkuse as main transcriptc.2806G>T p.Glu936Ter stop_gained 19/201 NM_032043.3 ENSP00000259008 P2Q9BX63-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.084
N
MutationTaster
Benign
1.0
A;D
Vest4
0.82
GERP RS
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.72
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.72
Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-59763296; API