6-131839315-A-G

Position:

• chr6-131839315-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.241-8461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,096 control chromosomes in the GnomAD database, including 17,049 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 (17049 hom., cov: 30)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.241-8461A>G		intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.241-8461A>G		intron_variant			NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5	c.241-8461A>G		intron_variant, NMD_transcript_variant		5		ENSP00000422424
ENPP1	ENST00000650507.1	c.*77-8461A>G		intron_variant, NMD_transcript_variant				ENSP00000497375
ENPP1	ENST00000486853.1	n.261-8461A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70124 AN: 150980 Hom.: 17028 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.465 AC: 70209 AN: 151096 Hom.: 17049 Cov.: 30 AF XY: 0.470 AC XY: 34703 AN XY: 73766

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.460

Alfa AF: 0.399 Hom.: 25484

Bravo AF: 0.458

Asia WGS AF: 0.434 AC: 1507 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.58
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: rs858341; hg19: chr6-132160455;