1-190186503-C-T

Position:

• chr1-190186503-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.962-25613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,018 control chromosomes in the GnomAD database, including 10,381 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 0.37 (10381 hom., cov: 33)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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 (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.962-25613G>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.962-25613G>A		intron_variant		1	NM_199051.3	ENSP00000356432.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55957 AN: 151900 Hom.: 10376 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.368 AC: 55994 AN: 152018 Hom.: 10381 Cov.: 33 AF XY: 0.366 AC XY: 27172 AN XY: 74278

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.341

Alfa AF: 0.366 Hom.: 20835

Bravo AF: 0.362

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.57

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: rs815343; hg19: chr1-190155633; COSMIC: COSV66517643;