rs6926970

Positions:

• chr6-131846150-C-A
• chr6-131846150-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.241-1626C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,952 control chromosomes in the GnomAD database, including 11,792 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 0.31 (11792 hom., cov: 31)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP1	NM_006208.3	c.241-1626C>A		intron_variant		ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP1	ENST00000647893.1	c.241-1626C>A		intron_variant			NM_006208.3	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46465 AN: 151836 Hom.: 11746 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.306 AC: 46570 AN: 151952 Hom.: 11792 Cov.: 31 AF XY: 0.300 AC XY: 22301 AN XY: 74280

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0934

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.277

Alfa AF: 0.166 Hom.: 3937

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.52

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: rs6926970; hg19: chr6-132167290;