17-61758503-T-G

Variant names:

• chr17-61758503-T-G
• rs2191249
• NM_032043.3:c.2098-13912A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032043.3(BRIP1):​c.2098-13912A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,156 control chromosomes in the GnomAD database, including 48,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48236 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2098-13912A>C		intron_variant	Intron 14 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2098-13912A>C		intron_variant	Intron 14 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120226 AN: 152038 Hom.: 48202 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.791 AC: 120308 AN: 152156 Hom.: 48236 Cov.: 32 AF XY: 0.790 AC XY: 58774 AN XY: 74386

African (AFR) AF: 0.893 AC: 37074 AN: 41518

American (AMR) AF: 0.632 AC: 9651 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2493 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4195 AN: 5174

South Asian (SAS) AF: 0.793 AC: 3828 AN: 4826

European-Finnish (FIN) AF: 0.834 AC: 8826 AN: 10582

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51570 AN: 67994

Other (OTH) AF: 0.772 AC: 1633 AN: 2114

Alfa AF: 0.764 Hom.: 22875

Bravo AF: 0.777

Asia WGS AF: 0.806 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.53
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2191249; hg19: chr17-59835864;