rs11079454

chr17-61679808-T-Achr17-61679808-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032043.3(BRIP1):c.*3488A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,056 control chromosomes in the GnomAD database, including 8,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (8865 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-61679808-T-A is Benign according to our data. Variant chr17-61679808-T-A is described in ClinVar as [Benign]. Clinvar id is 324294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRIP1	NM_032043.3	c.*3488A>T		3_prime_UTR_variant	20/20	ENST00000259008.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRIP1	ENST00000259008.7	c.*3488A>T		3_prime_UTR_variant	20/20	1	NM_032043.3	P2
BRIP1	ENST00000682755.1	c.*3488A>T		3_prime_UTR_variant	18/18

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51285 AN: 151938 Hom.: 8857 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51336 AN: 152056 Hom.: 8865 Cov.: 31 AF XY: 0.332 AC XY: 24687 AN XY: 74332

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.358

Alfa AF: 0.185 Hom.: 367

Bravo AF: 0.343

Asia WGS AF: 0.334 AC: 1160 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.73
Cadd	Benign	7.0
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11079454; hg19: chr17-59757169;