Variant 17-61863458-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032043.3(BRIP1):c.-205G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,882 control chromosomes in the GnomAD database, including 15,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15228 hom., cov: 29)

Exomes 𝑓: 0.47 ( 24 hom. )

Consequence

BRIP1
NM_032043.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.615

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-61863458-C-T is Benign according to our data. Variant chr17-61863458-C-T is described in ClinVar as [Benign]. Clinvar id is 324354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61863458-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3 linkuse as main transcript	c.-205G>A		5_prime_UTR_variant	1/20	ENST00000259008.7	NP_114432.2	Q9BX63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7 linkuse as main transcript	c.-205G>A		5_prime_UTR_variant	1/20	1	NM_032043.3	ENSP00000259008.2		Q9BX63-1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64667

AN:

151538

Hom.:

15209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.469

AC:

106

AN:

226

Hom.:

Cov.:

AF XY:

0.488

AC XY:

AN XY:

170

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.750

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.700

GnomAD4 genome

AF:

0.427

AC:

64724

AN:

151656

Hom.:

15228

Cov.:

AF XY:

0.439

AC XY:

32548

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.798

Gnomad4 SAS

AF:

0.671

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.447

Hom.:

31103

Bravo

AF:

0.419

Asia WGS

AF:

0.680

AC:

2364

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Fanconi anemia complementation group J

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.5

DANN

Benign

0.62

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