17-61852376-A-G

Variant names:

• chr17-61852376-A-G
• rs12937080
• NM_032043.3:c.380-3120T>C

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.380-3120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 152,250 control chromosomes in the GnomAD database, including 60 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 0.022 (60 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 8 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).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0221 (3363/152250) while in subpopulation AMR AF = 0.036 (550/15290). AF 95% confidence interval is 0.0335. There are 60 homozygotes in GnomAd4. There are 1554 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.380-3120T>C		intron_variant	Intron 4 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.380-3120T>C		intron_variant	Intron 4 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3364 AN: 152132 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0221 AC: 3363 AN: 152250 Hom.: 60 Cov.: 32 AF XY: 0.0209 AC XY: 1554 AN XY: 74454

African (AFR) AF: 0.00580 AC: 241 AN: 41548

American (AMR) AF: 0.0360 AC: 550 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4818

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0318 AC: 2163 AN: 68016

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0280 Hom.: 41

Bravo AF: 0.0254

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		1.2
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: rs12937080; hg19: chr17-59929737;