chr1-190413665-A-C

Position:

• chr1-190413665-A-C

Variant summary

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

The NM_199051.3(BRINP3):​c.236+40990T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,060 control chromosomes in the GnomAD database, including 2,222 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 0.17 (2222 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+40990T>G		intron_variant		ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.236+40990T>G		intron_variant		1	NM_199051.3	ENSP00000356432	P1
BRINP3	ENST00000631494.1	c.236+40990T>G		intron_variant		4		ENSP00000487601

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25470 AN: 151942 Hom.: 2218 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.168 AC: 25488 AN: 152060 Hom.: 2222 Cov.: 31 AF XY: 0.170 AC XY: 12611 AN XY: 74310

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.135

Alfa AF: 0.176 Hom.: 593

Bravo AF: 0.156

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.57

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: rs4845237; hg19: chr1-190382795;