rs12937080

Positions:

• chr17-61852376-A-G
• chr17-61852376-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.380-3120T>C		intron_variant		ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.380-3120T>C		intron_variant		1	NM_032043.3	ENSP00000259008	P2

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

Gnomad4 AFR AF: 0.00580

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0264 Hom.: 32

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12937080; hg19: chr17-59929737;