chr1-190413665-A-C

Variant names:

• chr1-190413665-A-C
• rs4845237
• NM_199051.3:c.236+40990T>G

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+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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+40990T>G		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+40990T>G		intron_variant	Intron 2 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.236+40990T>G		intron_variant	Intron 2 of 3	4		ENSP00000487601.1

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

African (AFR) AF: 0.123 AC: 5088 AN: 41484

American (AMR) AF: 0.128 AC: 1950 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3468

East Asian (EAS) AF: 0.148 AC: 760 AN: 5136

South Asian (SAS) AF: 0.201 AC: 969 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2589 AN: 10554

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12955 AN: 67992

Other (OTH) AF: 0.135 AC: 285 AN: 2106

Alfa AF: 0.175 Hom.: 601

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
PhyloP100		0.074
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: rs4845237; hg19: chr1-190382795;