rs876660519

chr17-61780875-G-Achr17-61780875-G-Cchr17-61780875-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032043.3(BRIP1):c.1759C>T(p.His587Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. H587D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18232858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.1759C>T	p.His587Tyr	missense_variant	12/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.1759C>T	p.His587Tyr	missense_variant	12/20	1	NM_032043.3	P2

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	0.077
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	17
Dann	Benign	0.90
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0079
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.95	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.075
Sift	Benign	0.73	T;.
Sift4G	Benign	0.69	T;T
Polyphen		0.048	B;.
Vest4		0.37
MutPred		0.53		Gain of methylation at K583 (P = 0.0645);Gain of methylation at K583 (P = 0.0645);
MVP		0.21
MPC		0.20
ClinPred		0.17	T
GERP RS		3.3
Varity_R		0.055
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr17-59858236; COSMIC: COSV51996438; COSMIC: COSV51996438;