chr1-190470338-A-T

Position:

• chr1-190470338-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199051.3(BRINP3):​c.-51+7110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 150,680 control chromosomes in the GnomAD database, including 11,645 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 0.37 (11645 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.-51+7110T>A		intron_variant		ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.-51+7110T>A		intron_variant		1	NM_199051.3	ENSP00000356432	P1
BRINP3	ENST00000445957.2	c.-51+4070T>A		intron_variant		3		ENSP00000393441
BRINP3	ENST00000631494.1	c.-51+5442T>A		intron_variant		4		ENSP00000487601

Frequencies

GnomAD3 genomes AF: 0.371 AC: 55838 AN: 150562 Hom.: 11654 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.370 AC: 55817 AN: 150680 Hom.: 11645 Cov.: 32 AF XY: 0.371 AC XY: 27313 AN XY: 73658

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.410

Alfa AF: 0.409 Hom.: 1689

Bravo AF: 0.355

Asia WGS AF: 0.351 AC: 1208 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.52

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: rs10494634; hg19: chr1-190439468; COSMIC: COSV66528011;