rs1830971

Positions:

• chr6-131827213-A-G

Variant summary

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

The NM_006208.3(ENPP1):​c.240+18938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 868,464 control chromosomes in the GnomAD database, including 69,757 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 0.37 (10884 hom., cov: 33)
  • Exomes 𝑓: 0.40 (58873 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482

Genes affected

ENPP1 (HGNC:3356): (ectonucleotide pyrophosphatase/phosphodiesterase 1) This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP1	NM_006208.3	c.240+18938A>G		intron_variant		ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP1	ENST00000647893.1	c.240+18938A>G		intron_variant			NM_006208.3	P1
	ENST00000455305.1	n.1201T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56460 AN: 151980 Hom.: 10885 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.402 AC: 288003 AN: 716366 Hom.: 58873 Cov.: 9 AF XY: 0.404 AC XY: 154988 AN XY: 383746

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.371 AC: 56472 AN: 152098 Hom.: 10884 Cov.: 33 AF XY: 0.367 AC XY: 27271 AN XY: 74356

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.398

Alfa AF: 0.401 Hom.: 4778

Bravo AF: 0.363

Asia WGS AF: 0.425 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.16
DANN	Benign	0.47

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: rs1830971; hg19: chr6-132148353; COSMIC: COSV62937901;