chr17-61683595-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032043.3(BRIP1):​c.3451G>C​(p.Glu1151Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1151K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BRIP1
NM_032043.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

1 publications found
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]
BRIP1 Gene-Disease associations (from GenCC):
  • familial ovarian cancer
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • Fanconi anemia
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
  • Fanconi anemia complementation group J
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hereditary breast carcinoma
    Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • colorectal adenoma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12245867).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRIP1NM_032043.3 linkc.3451G>C p.Glu1151Gln missense_variant Exon 20 of 20 ENST00000259008.7 NP_114432.2 Q9BX63-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRIP1ENST00000259008.7 linkc.3451G>C p.Glu1151Gln missense_variant Exon 20 of 20 1 NM_032043.3 ENSP00000259008.2 Q9BX63-1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
12
DANN
Benign
0.97
DEOGEN2
Benign
0.094
T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
1.4
L
PhyloP100
1.4
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.61
N
REVEL
Benign
0.15
Sift
Benign
0.15
T
Sift4G
Benign
0.25
T
Polyphen
0.50
P
Vest4
0.029
MutPred
0.16
Gain of solvent accessibility (P = 0.0081);
MVP
0.78
MPC
0.17
ClinPred
0.12
T
GERP RS
3.6
Varity_R
0.066
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1555572587; hg19: chr17-59760956; API