rs57694932

chr1-190470182-A-Gchr1-190470182-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_199051.3(BRINP3):c.-51+7266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 150,920 control chromosomes in the GnomAD database, including 1,050 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 0.11 (1050 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.-51+7266T>C		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.-51+7266T>C		intron_variant		1	NM_199051.3	P1
BRINP3	ENST00000445957.2	c.-51+4226T>C		intron_variant		3
BRINP3	ENST00000631494.1	c.-51+5598T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17027 AN: 150802 Hom.: 1050 Cov.: 32

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.113 AC: 17034 AN: 150920 Hom.: 1050 Cov.: 32 AF XY: 0.114 AC XY: 8433 AN XY: 73822

Gnomad4 AFR AF: 0.0978

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0801

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.127

Alfa AF: 0.108 Hom.: 198

Bravo AF: 0.120

Asia WGS AF: 0.138 AC: 478 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	19
Dann	Benign	0.81

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: rs57694932; hg19: chr1-190439312;