rs60657820

Positions:

• chr17-61681206-C-G

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.*2090G>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 0.372 in 199,364 control chromosomes in the GnomAD database, including 14,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11484 hom., cov: 31)
  • Exomes 𝑓: 0.35 (2976 hom.)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.505

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=-1.02).
• BP6: Variant 17-61681206-C-G is Benign according to our data. Variant chr17-61681206-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 210533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.*2090G>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.*2090G>C		3_prime_UTR_variant	20/20	1	NM_032043.3	P2
BRIP1	ENST00000682755.1	c.*2090G>C		3_prime_UTR_variant	18/18

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57556 AN: 151414 Hom.: 11465 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.347 AC: 16615 AN: 47830 Hom.: 2976 AF XY: 0.346 AC XY: 7671 AN XY: 22152

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.380 AC: 57628 AN: 151534 Hom.: 11484 Cov.: 31 AF XY: 0.373 AC XY: 27611 AN XY: 74068

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.381

Alfa AF: 0.217 Hom.: 442

Bravo AF: 0.394

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 29, 2015

- -

Fanconi anemia complementation group J Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60657820; hg19: chr17-59758567;