Variant 17-61685986-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PM2PM5BP4_StrongBP6_Moderate

The ENST00000259008.7(BRIP1):c.2755T>A(p.Ser919Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S919P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

BRIP1
ENST00000259008.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

Variant links:

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]

BRIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-61685986-A-GG is described in ClinVar as [Pathogenic]. Clinvar id is 1795606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.066113025).

BP6

Variant 17-61685986-A-T is Benign according to our data. Variant chr17-61685986-A-T is described in ClinVar as [Benign]. Clinvar id is 1221357.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3 linkuse as main transcript	c.2755T>A	p.Ser919Thr	missense_variant	19/20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7 linkuse as main transcript	c.2755T>A	p.Ser919Thr	missense_variant	19/20	1	NM_032043.3	ENSP00000259008	P2	Q9BX63-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151864

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74128

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.2

DANN

Benign

0.11

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.039

Sift

Benign

1.0

T;.

Sift4G

Benign

0.93

T;T

Vest4

0.11

MutPred

0.26

Gain of glycosylation at S919 (P = 0.0397);Gain of glycosylation at S919 (P = 0.0397);

MVP

0.36

MPC

0.16

ClinPred

0.072

GERP RS

0.71

Varity_R

0.038

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over