1-190202510-G-C

Variant summary

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

The NM_199051.3(BRINP3):c.961+23572C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,830 control chromosomes in the GnomAD database, including 13,858 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 0.42 (13858 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP3	NM_199051.3	c.961+23572C>G		intron_variant		ENST00000367462.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP3	ENST00000367462.5	c.961+23572C>G		intron_variant		1	NM_199051.3	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64231 AN: 151712 Hom.: 13855 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.423 AC: 64259 AN: 151830 Hom.: 13858 Cov.: 31 AF XY: 0.423 AC XY: 31368 AN XY: 74174

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.396

Alfa AF: 0.422 Hom.: 1689

Bravo AF: 0.406

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.27
Dann	Benign	0.44

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: rs2265670; hg19: chr1-190171640;