rs12724000

Variant names:

• chr1-190382547-C-T
• rs12724000
• NM_199051.3:c.236+72108G>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.236+72108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,012 control chromosomes in the GnomAD database, including 2,438 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 0.18 (2438 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+72108G>A		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.236+72108G>A		intron_variant	Intron 2 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.236+72108G>A		intron_variant	Intron 2 of 3	4		ENSP00000487601.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27169 AN: 151894 Hom.: 2434 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.179 AC: 27179 AN: 152012 Hom.: 2438 Cov.: 32 AF XY: 0.181 AC XY: 13438 AN XY: 74290

African (AFR) AF: 0.163 AC: 6739 AN: 41462

American (AMR) AF: 0.127 AC: 1931 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3466

East Asian (EAS) AF: 0.150 AC: 776 AN: 5164

South Asian (SAS) AF: 0.205 AC: 986 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2591 AN: 10562

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

European-Non Finnish (NFE) AF: 0.191 AC: 12956 AN: 67968

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.181 Hom.: 2136

Bravo AF: 0.167

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.77
PhyloP100		-1.1
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: rs12724000; hg19: chr1-190351677;