17-61807985-T-G

Variant names:

• chr17-61807985-T-G
• rs6504072
• NM_032043.3:c.918+482A>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.918+482A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,026 control chromosomes in the GnomAD database, including 47,699 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 (47699 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032043.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	NM_032043.3	MANE Select	c.918+482A>C		intron	N/A	NP_114432.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.918+482A>C		intron	N/A	ENSP00000259008.2
	BRIP1	ENST00000682453.1		c.918+482A>C		intron	N/A	ENSP00000506943.1
	BRIP1	ENST00000683039.1		c.918+482A>C		intron	N/A	ENSP00000508303.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119641 AN: 151908 Hom.: 47678 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.787 AC: 119707 AN: 152026 Hom.: 47699 Cov.: 32 AF XY: 0.787 AC XY: 58477 AN XY: 74292

African (AFR) AF: 0.874 AC: 36270 AN: 41494

American (AMR) AF: 0.637 AC: 9729 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2501 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4266 AN: 5186

South Asian (SAS) AF: 0.797 AC: 3830 AN: 4808

European-Finnish (FIN) AF: 0.831 AC: 8779 AN: 10562

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51663 AN: 67924

Other (OTH) AF: 0.772 AC: 1628 AN: 2108

Alfa AF: 0.735 Hom.: 2506

Bravo AF: 0.773

Asia WGS AF: 0.802 AC: 2766 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.090
DANN	Benign	0.48
PhyloP100		-1.3
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: rs6504072; hg19: chr17-59885346;