rs1555609387

chr17-61808751-C-Achr17-61808751-C-Gchr17-61808751-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032043.3(BRIP1):c.634G>T(p.Gly212Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G212S) 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: 1.62

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 3 ACMG points.

• 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	UniProt
BRIP1	NM_032043.3	c.634G>T	p.Gly212Cys	missense_variant	7/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.634G>T	p.Gly212Cys	missense_variant	7/20	1	NM_032043.3	P2

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0063	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.22
Sift	Benign	0.10	T;.
Sift4G	Uncertain	0.031	D;D
Polyphen		0.91	P;.
Vest4		0.48
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);
MVP		0.92
MPC		0.56
ClinPred		0.75	D
GERP RS		3.4
Varity_R		0.15
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.61		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.61		Position offset: -14

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: chr17-59886112;