rs12076854

Positions:

• chr1-190165941-T-A
• chr1-190165941-T-C

Variant summary

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

The NM_199051.3(BRINP3):​c.962-5051A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,032 control chromosomes in the GnomAD database, including 3,150 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 0.16 (3150 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.962-5051A>T		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.962-5051A>T		intron_variant		1	NM_199051.3	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24235 AN: 151912 Hom.: 3126 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.160 AC: 24308 AN: 152032 Hom.: 3150 Cov.: 32 AF XY: 0.162 AC XY: 12030 AN XY: 74330

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.168

Alfa AF: 0.0410 Hom.: 64

Bravo AF: 0.179

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.38

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: rs12076854; hg19: chr1-190135071;