rs2990996

Variant names:

• chr1-190176097-A-C
• rs2990996
• NM_199051.3:c.962-15207T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-190176097-A-C
• chr1-190176097-A-T

Variant summary

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

The NM_199051.3(BRINP3):​c.962-15207T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,002 control chromosomes in the GnomAD database, including 22,599 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 0.53 (22599 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 2 publications found

Genes affected

BRINP3 (HGNC:22393): (BMP/retinoic acid inducible neural specific 3) This gene is overexpressed in pituitary tumors but is underexpressed in tongue squamous cell carcinomas, ulcerative colitis, and peri-implantitis. Polymorphisms that increase expression of this gene have been shown to increase vascular inflammation, and an association of this gene with myocardial infarction has been demonstrated. Finally, hypermethylation of this gene may find usefulness as a biomarker for gastric cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.962-15207T>G		intron_variant	Intron 6 of 7	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.962-15207T>G		intron_variant	Intron 6 of 7	1	NM_199051.3	ENSP00000356432.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80292 AN: 151884 Hom.: 22556 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.529 AC: 80401 AN: 152002 Hom.: 22599 Cov.: 32 AF XY: 0.529 AC XY: 39280 AN XY: 74290

African (AFR) AF: 0.744 AC: 30855 AN: 41490

American (AMR) AF: 0.470 AC: 7160 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1572 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2554 AN: 5150

South Asian (SAS) AF: 0.561 AC: 2701 AN: 4812

European-Finnish (FIN) AF: 0.420 AC: 4439 AN: 10560

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29279 AN: 67970

Other (OTH) AF: 0.510 AC: 1072 AN: 2104

Alfa AF: 0.510 Hom.: 4131

Bravo AF: 0.541

Asia WGS AF: 0.527 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.43
PhyloP100		-0.44
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: rs2990996; hg19: chr1-190145227; COSMIC: COSV66517633;