rs774586397

Positions:

• chr17-61859893-T-A
• chr17-61859893-T-C
• chr17-61859893-T-G

Variant summary

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

The NM_032043.3(BRIP1):​c.108A>T​(p.Leu36Phe) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.108A>T	p.Leu36Phe	missense_variant	3/20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.108A>T	p.Leu36Phe	missense_variant	3/20	1	NM_032043.3	ENSP00000259008	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.57	D;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	M;M;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0060	D;.;.
Sift4G	Uncertain	0.0090	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.79
MutPred		0.64		Gain of ubiquitination at K39 (P = 0.1165);Gain of ubiquitination at K39 (P = 0.1165);Gain of ubiquitination at K39 (P = 0.1165);
MVP		0.71
MPC		0.71
ClinPred		0.91	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-59937254;