chr6-131821758-G-A

Position:

• chr6-131821758-G-A

Variant summary

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

The NM_006208.3(ENPP1):​c.240+13483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,932 control chromosomes in the GnomAD database, including 3,630 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 0.20 (3630 hom., cov: 32)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.240+13483G>A		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+13483G>A		intron_variant			NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5	c.240+13483G>A		intron_variant, NMD_transcript_variant		5		ENSP00000422424
ENPP1	ENST00000650507.1	c.154-4264G>A		intron_variant, NMD_transcript_variant				ENSP00000497375
ENPP1	ENST00000486853.1	n.260+13483G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30527 AN: 151814 Hom.: 3626 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.201 AC: 30551 AN: 151932 Hom.: 3630 Cov.: 32 AF XY: 0.196 AC XY: 14586 AN XY: 74262

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.185

Alfa AF: 0.110 Hom.: 198

Bravo AF: 0.209

Asia WGS AF: 0.171 AC: 596 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	0.032
DANN	Benign	0.60

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: rs12201710; hg19: chr6-132142898;