rs7775386

chr6-131836009-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.241-11767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,054 control chromosomes in the GnomAD database, including 5,932 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 0.24 (5932 hom., cov: 32)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP1	NM_006208.3	c.241-11767C>T		intron_variant		ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP1	ENST00000647893.1	c.241-11767C>T		intron_variant			NM_006208.3	P1
ENPP1	ENST00000513998.5	c.241-11767C>T		intron_variant, NMD_transcript_variant		5
ENPP1	ENST00000650507.1	c.*76+9894C>T		intron_variant, NMD_transcript_variant
ENPP1	ENST00000486853.1	n.261-11767C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36043 AN: 151938 Hom.: 5918 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.238 AC: 36118 AN: 152054 Hom.: 5932 Cov.: 32 AF XY: 0.234 AC XY: 17365 AN XY: 74318

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.217

Alfa AF: 0.156 Hom.: 3714

Bravo AF: 0.253

Asia WGS AF: 0.185 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.72

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: rs7775386; hg19: chr6-132157149;