1-190458964-A-T

Variant names:

• chr1-190458964-A-T
• rs10920722
• NM_199051.3:c.-50-4024T>A

Variant summary

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

The NM_199051.3(BRINP3):​c.-50-4024T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,812 control chromosomes in the GnomAD database, including 2,837 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 0.19 (2837 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.-50-4024T>A		intron_variant	Intron 1 of 7	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.-50-4024T>A		intron_variant	Intron 1 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.-50-4024T>A		intron_variant	Intron 1 of 3	4		ENSP00000487601.1
BRINP3	ENST00000445957.2	c.-50-4024T>A		intron_variant	Intron 1 of 1	3		ENSP00000393441.2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28778 AN: 151694 Hom.: 2826 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.190 AC: 28817 AN: 151812 Hom.: 2837 Cov.: 31 AF XY: 0.191 AC XY: 14174 AN XY: 74180

African (AFR) AF: 0.161 AC: 6665 AN: 41480

American (AMR) AF: 0.183 AC: 2793 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3460

East Asian (EAS) AF: 0.193 AC: 1001 AN: 5176

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2386 AN: 10548

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13509 AN: 67766

Other (OTH) AF: 0.165 AC: 347 AN: 2104

Alfa AF: 0.190 Hom.: 345

Bravo AF: 0.184

Asia WGS AF: 0.191 AC: 660 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.16
PhyloP100		1.4
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: rs10920722; hg19: chr1-190428094;