17-61716051-G-C

Position:

• chr17-61716051-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032043.3(BRIP1):​c.2392C>G​(p.Arg798Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2392C>G	p.Arg798Gly	missense_variant	17/20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2392C>G	p.Arg798Gly	missense_variant	17/20	1	NM_032043.3	ENSP00000259008	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.9	D;.
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.52		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		1.0
MPC		0.71
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.89
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs137852986; hg19: chr17-59793412;