17-61680480-C-CTTTCTTT

Variant names:

• chr17-61680480-C-CTTTCTTT
• rs1555571892
• NM_032043.3:c.*2815_*2816insAAAGAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_032043.3(BRIP1):​c.*2815_*2816insAAAGAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.055 (520 hom., cov: 0)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.0550
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.*2815_*2816insAAAGAAA		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.*2815_*2816insAAAGAAA		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2
BRIP1	ENST00000682755.1	c.*2815_*2816insAAAGAAA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000507660.1

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 6836 AN: 123838 Hom.: 524 Cov.: 0

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.0841

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0811

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.126

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0551 AC: 6827 AN: 123814 Hom.: 520 Cov.: 0 AF XY: 0.0587 AC XY: 3429 AN XY: 58414

African (AFR) AF: 0.0198 AC: 629 AN: 31710

American (AMR) AF: 0.0498 AC: 566 AN: 11364

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 261 AN: 3220

East Asian (EAS) AF: 0.154 AC: 631 AN: 4110

South Asian (SAS) AF: 0.218 AC: 856 AN: 3932

European-Finnish (FIN) AF: 0.0656 AC: 350 AN: 5334

Middle Eastern (MID) AF: 0.131 AC: 26 AN: 198

European-Non Finnish (NFE) AF: 0.0542 AC: 3330 AN: 61478

Other (OTH) AF: 0.0659 AC: 107 AN: 1624

Alfa AF: 0.0145 Hom.: 66

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breast neoplasm Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs1555571892; hg19: chr17-59757841;