rs1206684

Variant names:

• chr6-131633739-G-A
• rs1206684
• ENST00000414305.5:c.-150-3496G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414305.5(ENPP3):​c.-150-3496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,076 control chromosomes in the GnomAD database, including 8,499 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 0.30 (8499 hom., cov: 32)
• Consequence: ENPP3 ENST00000414305.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 5 publications found

Genes affected

ENPP3 (HGNC:3358): (ectonucleotide pyrophosphatase/phosphodiesterase 3) The protein encoded by this gene belongs to a series of ectoenzymes that are involved in hydrolysis of extracellular nucleotides. These ectoenzymes possess ATPase and ATP pyrophosphatase activities and are type II transmembrane proteins. Expression of the related rat mRNA has been found in a subset of immature glial cells and in the alimentary tract. The corresponding rat protein has been detected in the pancreas, small intestine, colon, and liver. The human mRNA is expressed in glioma cells, prostate, and uterus. Expression of the human protein has been detected in uterus, basophils, and mast cells. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP3	ENST00000414305.5	c.-150-3496G>A		intron_variant	Intron 1 of 25	1		ENSP00000406261.1
ENPP3	ENST00000427707.5	n.-150-3496G>A		intron_variant	Intron 1 of 11	1		ENSP00000415589.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46063 AN: 151958 Hom.: 8498 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.303 AC: 46066 AN: 152076 Hom.: 8499 Cov.: 32 AF XY: 0.306 AC XY: 22748 AN XY: 74322

African (AFR) AF: 0.0803 AC: 3334 AN: 41504

American (AMR) AF: 0.348 AC: 5327 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2530 AN: 5172

South Asian (SAS) AF: 0.441 AC: 2120 AN: 4808

European-Finnish (FIN) AF: 0.373 AC: 3930 AN: 10538

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26192 AN: 67984

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.366 Hom.: 17386

Bravo AF: 0.290

Asia WGS AF: 0.492 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		1.5
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: rs1206684; hg19: chr6-131954879;