rs4633293

Variant names:

• chr1-190225779-A-G
• rs4633293
• NM_199051.3:c.961+303T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-190225779-A-G
• chr1-190225779-A-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.961+303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,656 control chromosomes in the GnomAD database, including 24,822 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 0.57 (24822 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.961+303T>C		intron_variant	Intron 6 of 7	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.961+303T>C		intron_variant	Intron 6 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000463404.1	n.115+303T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86247 AN: 151536 Hom.: 24789 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.569 AC: 86331 AN: 151656 Hom.: 24822 Cov.: 31 AF XY: 0.569 AC XY: 42133 AN XY: 74072

African (AFR) AF: 0.528 AC: 21884 AN: 41412

American (AMR) AF: 0.686 AC: 10414 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2274 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3299 AN: 5120

South Asian (SAS) AF: 0.653 AC: 3148 AN: 4822

European-Finnish (FIN) AF: 0.464 AC: 4891 AN: 10536

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.569 AC: 38558 AN: 67812

Other (OTH) AF: 0.609 AC: 1284 AN: 2110

Alfa AF: 0.587 Hom.: 31134

Bravo AF: 0.584

Asia WGS AF: 0.654 AC: 2270 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.40
PhyloP100		-0.13
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: rs4633293; hg19: chr1-190194909;