rs12142564

Positions:

• chr1-190102873-C-T

Variant summary

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

The NM_199051.3(BRINP3):​c.1185-3739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 151,854 control chromosomes in the GnomAD database, including 855 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 0.10 (855 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.1185-3739G>A		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.1185-3739G>A		intron_variant		1	NM_199051.3	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15192 AN: 151736 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.100 AC: 15213 AN: 151854 Hom.: 855 Cov.: 32 AF XY: 0.102 AC XY: 7534 AN XY: 74226

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.115

Alfa AF: 0.102 Hom.: 198

Bravo AF: 0.0949

Asia WGS AF: 0.107 AC: 373 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.39

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: rs12142564; hg19: chr1-190072003;