chr6-131819872-C-T

Position:

• chr6-131819872-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.240+11597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 463,358 control chromosomes in the GnomAD database, including 92,657 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 0.65 (32212 hom., cov: 31)
  • Exomes 𝑓: 0.62 (60445 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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]

SELENOKP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.240+11597C>T		intron_variant		ENST00000647893.1	NP_006199.2
SELENOKP2		n.131819872C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.240+11597C>T		intron_variant			NM_006208.3	ENSP00000498074.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98061 AN: 151756 Hom.: 32194 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.667

GnomAD4 exome AF: 0.617 AC: 192243 AN: 311488 Hom.: 60445 Cov.: 2 AF XY: 0.622 AC XY: 108759 AN XY: 174994

Gnomad4 AFR exome AF: 0.720

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.824

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.646 AC: 98124 AN: 151870 Hom.: 32212 Cov.: 31 AF XY: 0.645 AC XY: 47891 AN XY: 74194

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.667

Alfa AF: 0.531 Hom.: 1630

Bravo AF: 0.646

Asia WGS AF: 0.748 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.59

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: rs943003; hg19: chr6-132141012;