chr17-61847251-G-C

Position:

• chr17-61847251-G-C

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.508-31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,610,738 control chromosomes in the GnomAD database, including 27,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2453 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24923 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.19

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-61847251-G-C is Benign according to our data. Variant chr17-61847251-G-C is described in ClinVar as [Benign]. Clinvar id is 262007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61847251-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.508-31C>G		intron_variant		ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.508-31C>G		intron_variant		1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24067 AN: 152014 Hom.: 2448 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.161

GnomAD3 exomes AF: 0.197 AC: 49391 AN: 250934 Hom.: 6423 AF XY: 0.194 AC XY: 26288 AN XY: 135706

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.556

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.270

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.172 AC: 250151 AN: 1458606 Hom.: 24923 Cov.: 32 AF XY: 0.171 AC XY: 123952 AN XY: 725860

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.525

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.158 AC: 24088 AN: 152132 Hom.: 2453 Cov.: 32 AF XY: 0.165 AC XY: 12281 AN XY: 74348

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.167

Alfa AF: 0.153 Hom.: 375

Bravo AF: 0.151

Asia WGS AF: 0.312 AC: 1084 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

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	- -

Familial cancer of breast Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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	-0.85
CADD	Benign	0.11
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4988344; hg19: chr17-59924612; COSMIC: COSV51994665;