6-131819736-C-T

Position:

• chr6-131819736-C-T

Variant summary

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

The NM_006208.3(ENPP1):​c.240+11461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 282,940 control chromosomes in the GnomAD database, including 1,416 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 0.10 (1059 hom., cov: 32)
  • Exomes 𝑓: 0.067 (357 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.240+11461C>T		intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.240+11461C>T		intron_variant			NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5	c.240+11461C>T		intron_variant, NMD_transcript_variant		5		ENSP00000422424
ENPP1	ENST00000650507.1	c.154-6286C>T		intron_variant, NMD_transcript_variant				ENSP00000497375
ENPP1	ENST00000486853.1	n.260+11461C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15469 AN: 152056 Hom.: 1055 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0669 AC: 8750 AN: 130768 Hom.: 357 AF XY: 0.0622 AC XY: 4421 AN XY: 71032

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0495

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0268

Gnomad4 SAS exome AF: 0.0428

Gnomad4 FIN exome AF: 0.0910

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0739

GnomAD4 genome AF: 0.102 AC: 15487 AN: 152172 Hom.: 1059 Cov.: 32 AF XY: 0.101 AC XY: 7487 AN XY: 74398

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0739

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0288

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0989

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0953

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.104

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.56

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: rs943004; hg19: chr6-132140876;