chr1-190423315-T-A

Variant names:

• chr1-190423315-T-A
• rs872177
• NM_199051.3:c.236+31340A>T

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+31340A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,394 control chromosomes in the GnomAD database, including 8,606 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 0.33 (8606 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+31340A>T		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+31340A>T		intron_variant	Intron 2 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.236+31340A>T		intron_variant	Intron 2 of 3	4		ENSP00000487601.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50378 AN: 151276 Hom.: 8582 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.333 AC: 50439 AN: 151394 Hom.: 8606 Cov.: 31 AF XY: 0.338 AC XY: 24965 AN XY: 73968

African (AFR) AF: 0.386 AC: 15953 AN: 41308

American (AMR) AF: 0.267 AC: 4041 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1169 AN: 5156

South Asian (SAS) AF: 0.315 AC: 1519 AN: 4822

European-Finnish (FIN) AF: 0.447 AC: 4703 AN: 10530

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20942 AN: 67680

Other (OTH) AF: 0.280 AC: 591 AN: 2108

Alfa AF: 0.333 Hom.: 1094

Bravo AF: 0.319

Asia WGS AF: 0.251 AC: 871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0080
DANN	Benign	0.27
PhyloP100		-3.6
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: rs872177; hg19: chr1-190392445; COSMIC: COSV66528005;