rs2191248

chr17-61798991-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032043.3(BRIP1):c.1340+109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,019,488 control chromosomes in the GnomAD database, including 54,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6259 hom., cov: 32)
  • Exomes 𝑓: 0.32 (47826 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.51

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-61798991-C-T is Benign according to our data. Variant chr17-61798991-C-T is described in ClinVar as [Benign]. Clinvar id is 1263501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61798991-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.1340+109G>A		intron_variant		ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.1340+109G>A		intron_variant		1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39216 AN: 151794 Hom.: 6266 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.323 AC: 279961 AN: 867576 Hom.: 47826 AF XY: 0.321 AC XY: 145689 AN XY: 453240

Gnomad4 AFR exome AF: 0.0725

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.258 AC: 39202 AN: 151912 Hom.: 6259 Cov.: 32 AF XY: 0.256 AC XY: 19016 AN XY: 74228

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.240

Alfa AF: 0.310 Hom.: 2751

Bravo AF: 0.237

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Hereditary breast ovarian cancer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	16
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs2191248; hg19: chr17-59876352; COSMIC: COSV51993315;