rs780024960

Variant names:

• chr17-61849141-T-A
• NM_032043.3:c.495A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61849141-T-A
• chr17-61849141-T-G

Variant summary

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

The NM_032043.3(BRIP1):​c.495A>T​(p.Glu165Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRIP1 NM_032043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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=0.23859122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.495A>T	p.Glu165Asp	missense_variant	Exon 5 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.495A>T	p.Glu165Asp	missense_variant	Exon 5 of 20	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 06, 2021

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Kwong 2020); This variant is associated with the following publications: (PMID: 32068069) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.041
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.53	N;.
REVEL	Benign	0.10
Sift	Benign	0.20	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.022	B;.
Vest4		0.47
MutPred		0.37		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.56
MPC		0.24
ClinPred		0.52	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr17-59926502;