rs2185836

chr1-190113464-A-G

Variant summary

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

The NM_199051.3(BRINP3):c.1185-14330T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,990 control chromosomes in the GnomAD database, including 13,351 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 0.40 (13351 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.1185-14330T>C		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.1185-14330T>C		intron_variant		1	NM_199051.3	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61371 AN: 151872 Hom.: 13346 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.404 AC: 61402 AN: 151990 Hom.: 13351 Cov.: 32 AF XY: 0.402 AC XY: 29826 AN XY: 74286

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.419

Alfa AF: 0.417 Hom.: 2197

Bravo AF: 0.382

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.9
Dann	Benign	0.70

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: rs2185836; hg19: chr1-190082594;