rs1978111

Positions:

• chr17-61683138-A-G
• chr17-61683138-A-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.*158T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 929,366 control chromosomes in the GnomAD database, including 170,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28545 hom., cov: 31)
  • Exomes 𝑓: 0.59 (141969 hom.)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.426

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=-0.84).
• BP6: Variant 17-61683138-A-G is Benign according to our data. Variant chr17-61683138-A-G is described in ClinVar as [Benign]. Clinvar id is 324344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.*158T>C		3_prime_UTR_variant	20/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.*158T>C		3_prime_UTR_variant	20/20	1	NM_032043.3	P2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92015 AN: 151786 Hom.: 28511 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.592 AC: 460403 AN: 777464 Hom.: 141969 Cov.: 10 AF XY: 0.587 AC XY: 232385 AN XY: 395888

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.606 AC: 92110 AN: 151902 Hom.: 28545 Cov.: 31 AF XY: 0.601 AC XY: 44628 AN XY: 74262

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.630

Alfa AF: 0.454 Hom.: 1244

Bravo AF: 0.636

Asia WGS AF: 0.534 AC: 1858 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group J Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.56

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: rs1978111; hg19: chr17-59760499;