6-131828160-C-G

Variant names:

• chr6-131828160-C-G
• rs1409181
• NM_006208.3:c.241-19616C>G

Variant summary

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

The NM_006208.3(ENPP1):​c.241-19616C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 576,310 control chromosomes in the GnomAD database, including 74,322 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 0.46 (16980 hom., cov: 32)
  • Exomes 𝑓: 0.52 (57342 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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]

ENSG00000237115 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.241-19616C>G		intron_variant	Intron 1 of 24	ENST00000647893.1	NP_006199.2
LOC100421775		n.131828160C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.241-19616C>G		intron_variant	Intron 1 of 24		NM_006208.3	ENSP00000498074.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70415 AN: 151878 Hom.: 16985 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.516 AC: 218760 AN: 424314 Hom.: 57342 Cov.: 3 AF XY: 0.526 AC XY: 125347 AN XY: 238464

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.463 AC: 70422 AN: 151996 Hom.: 16980 Cov.: 32 AF XY: 0.463 AC XY: 34395 AN XY: 74266

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.498

Alfa AF: 0.384 Hom.: 1166

Bravo AF: 0.449

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1409181; hg19: chr6-132149300;