rs114505031

chr17-61744613-A-Gchr17-61744613-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032043.3(BRIP1):c.2098-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,607,874 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (10 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.159

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=-0.83).
• BP6: Variant 17-61744613-A-G is Benign according to our data. Variant chr17-61744613-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 523693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61744613-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00635 (967/152286) while in subpopulation AFR AF= 0.0222 (923/41568). AF 95% confidence interval is 0.021. There are 8 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.2098-22T>C		intron_variant		ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.2098-22T>C		intron_variant		1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 965 AN: 152168 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

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: 0.0000147

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00163 AC: 408 AN: 250202 Hom.: 6 AF XY: 0.00113 AC XY: 153 AN XY: 135474

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000659

GnomAD4 exome AF: 0.000602 AC: 876 AN: 1455588 Hom.: 10 Cov.: 30 AF XY: 0.000496 AC XY: 359 AN XY: 724458

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000813

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00635 AC: 967 AN: 152286 Hom.: 8 Cov.: 32 AF XY: 0.00596 AC XY: 444 AN XY: 74462

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.00692

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.

Jan 16, 2018

- -

Hereditary breast ovarian cancer syndrome Benign:1

Likely 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	-0.83
Cadd	Benign	0.22
Dann	Benign	0.42

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: rs114505031; hg19: chr17-59821974;