rs8076727

Variant names:

• chr17-61837320-G-A
• rs8076727
• NM_032043.3:c.627+9781C>T

Variant summary

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

The NM_032043.3(BRIP1):​c.627+9781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,896 control chromosomes in the GnomAD database, including 3,312 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 0.19 (3312 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.627+9781C>T		intron_variant	Intron 6 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.627+9781C>T		intron_variant	Intron 6 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29400 AN: 151778 Hom.: 3305 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.194 AC: 29419 AN: 151896 Hom.: 3312 Cov.: 31 AF XY: 0.194 AC XY: 14398 AN XY: 74230

African (AFR) AF: 0.112 AC: 4647 AN: 41452

American (AMR) AF: 0.309 AC: 4709 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3468

East Asian (EAS) AF: 0.0287 AC: 148 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4812

European-Finnish (FIN) AF: 0.168 AC: 1771 AN: 10516

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15534 AN: 67914

Other (OTH) AF: 0.212 AC: 447 AN: 2108

Alfa AF: 0.218 Hom.: 919

Bravo AF: 0.200

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.58
PhyloP100		-0.58
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: rs8076727; hg19: chr17-59914681;