rs2134098

Positions:

• chr1-190425141-G-C

Variant summary

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

The NM_199051.3(BRINP3):​c.236+29514C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 151,632 control chromosomes in the GnomAD database, including 455 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 0.068 (455 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.236+29514C>G		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.236+29514C>G		intron_variant		1	NM_199051.3	P1
BRINP3	ENST00000631494.1	c.236+29514C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10373 AN: 151514 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0737

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0684 AC: 10370 AN: 151632 Hom.: 455 Cov.: 32 AF XY: 0.0679 AC XY: 5035 AN XY: 74134

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0989

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0837 Hom.: 73

Bravo AF: 0.0684

Asia WGS AF: 0.0330 AC: 117 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.37

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: rs2134098; hg19: chr1-190394271;