rs12724000

Positions:

• chr1-190382547-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.236+72108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,012 control chromosomes in the GnomAD database, including 2,438 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 0.18 (2438 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+72108G>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.236+72108G>A		intron_variant		1	NM_199051.3	ENSP00000356432	P1
BRINP3	ENST00000631494.1	c.236+72108G>A		intron_variant		4		ENSP00000487601

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27169 AN: 151894 Hom.: 2434 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.179 AC: 27179 AN: 152012 Hom.: 2438 Cov.: 32 AF XY: 0.181 AC XY: 13438 AN XY: 74290

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.145

Alfa AF: 0.183 Hom.: 1611

Bravo AF: 0.167

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.77

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: rs12724000; hg19: chr1-190351677;