17-61849272-TA-TAA

Position:

• chr17-61849272-TA-TAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_032043.3(BRIP1):​c.380-17_380-16insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00062 in 1,602,006 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (9 hom.)
• Consequence: BRIP1 NM_032043.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.0940

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 -16 ACMG points.

• BP6: Variant 17-61849272-T-TA is Benign according to our data. Variant chr17-61849272-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 182355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000637 (924/1450014) while in subpopulation MID AF= 0.00685 (37/5402). AF 95% confidence interval is 0.00511. There are 9 homozygotes in gnomad4_exome. There are 548 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.380-17_380-16insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.380-17_380-16insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_032043.3	ENSP00000259008	P2

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 70 AN: 151872 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000789

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.000960 AC: 231 AN: 240610 Hom.: 1 AF XY: 0.00114 AC XY: 148 AN XY: 130390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000740

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00478

Gnomad FIN exome AF: 0.0000473

Gnomad NFE exome AF: 0.000561

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.000637 AC: 924 AN: 1450014 Hom.: 9 Cov.: 30 AF XY: 0.000760 AC XY: 548 AN XY: 721338

Gnomad4 AFR exome AF: 0.0000610

Gnomad4 AMR exome AF: 0.000719

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.00435

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000366

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.000461 AC: 70 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.000471 AC XY: 35 AN XY: 74318

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000788

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00237

Bravo AF: 0.000359

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 17, 2017	- -

Hereditary cancer-predisposing syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Apr 07, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2014	The variant is found in BR-OV-HEREDIC,HEREDICANCER panel(s). -

Breast and/or ovarian cancer Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Jan 06, 2023

- -

Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Fanconi anemia complementation group J Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Counsyl

Jun 27, 2016

- -

Familial cancer of breast Benign:1

Benign, criteria provided, single submitter

clinical testing

Myriad Genetics, Inc.

Feb 28, 2023

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. -

Ovarian neoplasm Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Counsyl

Jun 27, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs545021924; hg19: chr17-59926633;