rs7213430

Variant names:

• chr17-61682813-G-A
• rs7213430
• NM_032043.3:c.*483C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61682813-G-A
• chr17-61682813-G-C

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.*483C>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 0.612 in 191,258 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28954 hom., cov: 32)
  • Exomes 𝑓: 0.62 (7621 hom.)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0250

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=-0.89).
• BP6: Variant 17-61682813-G-A is Benign according to our data. Variant chr17-61682813-G-A is described in ClinVar as [Benign]. Clinvar id is 324335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.*483C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008	c.*483C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92718 AN: 151952 Hom.: 28915 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.618 AC: 24215 AN: 39186 Hom.: 7621 Cov.: 0 AF XY: 0.613 AC XY: 11233 AN XY: 18338

Gnomad4 AFR exome AF: 0.646

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.610 AC: 92819 AN: 152072 Hom.: 28954 Cov.: 32 AF XY: 0.605 AC XY: 44944 AN XY: 74324

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.737

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: 0.598 Hom.: 24168

Bravo AF: 0.641

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26711789) -

Fanconi anemia complementation group J Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.89
CADD	Benign	2.7
DANN	Benign	0.28

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: rs7213430; hg19: chr17-59760174;