17-61803285-T-C

Variant names:

• chr17-61803285-T-C
• rs34289250
• NM_032043.3:c.919-1811A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032043.3(BRIP1):​c.919-1811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 152,280 control chromosomes in the GnomAD database, including 6 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 0.0078 (6 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 14 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00779 (1186/152280) while in subpopulation NFE AF = 0.0122 (833/68010). AF 95% confidence interval is 0.0116. There are 6 homozygotes in GnomAd4. There are 535 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

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.919-1811A>G		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.919-1811A>G		intron	N/A	ENSP00000259008.2
	BRIP1	ENST00000682453.1		c.919-1811A>G		intron	N/A	ENSP00000506943.1
	BRIP1	ENST00000683039.1		c.919-1811A>G		intron	N/A	ENSP00000508303.1

Frequencies

GnomAD3 genomes AF: 0.00779 AC: 1185 AN: 152162 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00812

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

GnomAD4 genome AF: 0.00779 AC: 1186 AN: 152280 Hom.: 6 Cov.: 32 AF XY: 0.00719 AC XY: 535 AN XY: 74458

African (AFR) AF: 0.00188 AC: 78 AN: 41582

American (AMR) AF: 0.00902 AC: 138 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 833 AN: 68010

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00934 Hom.: 0

Bravo AF: 0.00845

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.34
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism

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: rs34289250; hg19: chr17-59880646;