rs11079454

Variant names:

• chr17-61679808-T-A
• rs11079454
• NM_032043.3:c.*3488A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61679808-T-A
• chr17-61679808-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

BRIP1 Gene-Disease associations (from GenCC):

• familial ovarian cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Fanconi anemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
• Fanconi anemia complementation group J

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary breast carcinoma

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.*3488A>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	ENST00000259008.7	c.*3488A>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2
BRIP1	ENST00000682755.1	c.*3488A>T		3_prime_UTR_variant	Exon 18 of 18			ENSP00000507660.1

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

African (AFR) AF: 0.352 AC: 14604 AN: 41460

American (AMR) AF: 0.298 AC: 4560 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1059 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2542 AN: 5178

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4816

European-Finnish (FIN) AF: 0.243 AC: 2564 AN: 10568

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23597 AN: 67968

Other (OTH) AF: 0.358 AC: 757 AN: 2114

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

Jan 12, 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	-0.73
CADD	Benign	7.0
DANN	Benign	0.84
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs11079454; hg19: chr17-59757169;