chr6-131847222-G-A

Position:

• chr6-131847222-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.241-554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,120 control chromosomes in the GnomAD database, including 573 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 0.069 (573 hom., cov: 32)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.241-554G>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.241-554G>A		intron_variant			NM_006208.3	ENSP00000498074	P1

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10458 AN: 152002 Hom.: 565 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0653

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

GnomAD4 genome AF: 0.0690 AC: 10491 AN: 152120 Hom.: 573 Cov.: 32 AF XY: 0.0677 AC XY: 5034 AN XY: 74390

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0646

Alfa AF: 0.0586 Hom.: 55

Bravo AF: 0.0683

Asia WGS AF: 0.0370 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
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: rs7768555; hg19: chr6-132168362;