rs12140456

Positions:

• chr1-190243735-G-C
• chr1-190243735-G-T

Variant summary

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

The NM_199051.3(BRINP3):​c.619-9258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,956 control chromosomes in the GnomAD database, including 12,586 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 0.38 (12586 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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]

LOC105371659 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.619-9258C>G		intron_variant		ENST00000367462.5	NP_950252.1
LOC105371659	XR_922376.3	n.81-5878G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.619-9258C>G		intron_variant		1	NM_199051.3	ENSP00000356432	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58336 AN: 151838 Hom.: 12592 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.384 AC: 58326 AN: 151956 Hom.: 12586 Cov.: 32 AF XY: 0.383 AC XY: 28438 AN XY: 74252

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.406

Alfa AF: 0.298 Hom.: 888

Bravo AF: 0.377

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.64

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: rs12140456; hg19: chr1-190212865;