rs2490271

chr1-190473841-G-Achr1-190473841-G-C

Variant summary

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

The NM_199051.3(BRINP3):c.-51+3607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 150,600 control chromosomes in the GnomAD database, including 46,367 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 0.78 (46367 hom., cov: 27)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.-51+3607C>T		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.-51+3607C>T		intron_variant		1	NM_199051.3	P1
BRINP3	ENST00000445957.2	c.-51+567C>T		intron_variant		3
BRINP3	ENST00000631494.1	c.-51+1939C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 117910 AN: 150502 Hom.: 46340 Cov.: 27

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.779

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.783 AC: 117978 AN: 150600 Hom.: 46367 Cov.: 27 AF XY: 0.784 AC XY: 57620 AN XY: 73452

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.780

Alfa AF: 0.811 Hom.: 65359

Bravo AF: 0.774

Asia WGS AF: 0.711 AC: 2469 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.77
Dann	Benign	0.32

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: rs2490271; hg19: chr1-190442971;