rs2134098

Variant names:

• chr1-190425141-G-C
• rs2134098
• NM_199051.3:c.236+29514C>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+29514C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 151,632 control chromosomes in the GnomAD database, including 455 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 0.068 (455 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.236+29514C>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+29514C>G		intron_variant	Intron 2 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.236+29514C>G		intron_variant	Intron 2 of 3	4		ENSP00000487601.1

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10373 AN: 151514 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0737

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0684 AC: 10370 AN: 151632 Hom.: 455 Cov.: 32 AF XY: 0.0679 AC XY: 5035 AN XY: 74134

African (AFR) AF: 0.0183 AC: 760 AN: 41498

American (AMR) AF: 0.0835 AC: 1267 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 348 AN: 3460

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0795 AC: 383 AN: 4816

European-Finnish (FIN) AF: 0.0629 AC: 666 AN: 10590

Middle Eastern (MID) AF: 0.0724 AC: 21 AN: 290

European-Non Finnish (NFE) AF: 0.0989 AC: 6684 AN: 67608

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0837 Hom.: 73

Bravo AF: 0.0684

Asia WGS AF: 0.0330 AC: 117 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.37
PhyloP100		0.079
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: rs2134098; hg19: chr1-190394271;