1-190290531-T-C

Variant names:

• chr1-190290531-T-C
• rs480692
• NM_199051.3:c.237-8781A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199051.3(BRINP3):​c.237-8781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,946 control chromosomes in the GnomAD database, including 13,202 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 (13202 hom., cov: 33)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 0 publications found

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]

ENSG00000225811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.237-8781A>G		intron_variant	Intron 2 of 7	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.237-8781A>G		intron_variant	Intron 2 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.237-8781A>G		intron_variant	Intron 2 of 3	4		ENSP00000487601.1
ENSG00000225811	ENST00000452178.1	n.143-12172T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61047 AN: 151828 Hom.: 13207 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.402 AC: 61049 AN: 151946 Hom.: 13202 Cov.: 33 AF XY: 0.400 AC XY: 29729 AN XY: 74266

African (AFR) AF: 0.229 AC: 9489 AN: 41496

American (AMR) AF: 0.474 AC: 7229 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2025 AN: 5166

South Asian (SAS) AF: 0.387 AC: 1870 AN: 4826

European-Finnish (FIN) AF: 0.430 AC: 4545 AN: 10558

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33017 AN: 67878

Other (OTH) AF: 0.417 AC: 879 AN: 2108

Alfa AF: 0.462 Hom.: 20556

Bravo AF: 0.396

Asia WGS AF: 0.399 AC: 1388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.39
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs480692; hg19: chr1-190259661;