6-131819736-C-T

Variant names:

• chr6-131819736-C-T
• rs943004
• NM_006208.3:c.240+11461C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006208.3(ENPP1):​c.240+11461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 282,940 control chromosomes in the GnomAD database, including 1,416 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 0.10 (1059 hom., cov: 32)
  • Exomes 𝑓: 0.067 (357 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 2 publications found

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:53725): (selenoprotein K pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	NM_006208.3	MANE Select	c.240+11461C>T		intron	N/A	NP_006199.2	P22413

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	ENST00000647893.1	MANE Select	c.240+11461C>T		intron	N/A	ENSP00000498074.1	P22413
	ENPP1	ENST00000922186.1		c.240+11461C>T		intron	N/A	ENSP00000592245.1
	ENPP1	ENST00000486853.1	TSL:2	n.260+11461C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15469 AN: 152056 Hom.: 1055 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0669 AC: 8750 AN: 130768 Hom.: 357 AF XY: 0.0622 AC XY: 4421 AN XY: 71032

African (AFR) AF: 0.189 AC: 395 AN: 2088

American (AMR) AF: 0.0495 AC: 171 AN: 3454

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 322 AN: 2840

East Asian (EAS) AF: 0.0268 AC: 104 AN: 3884

South Asian (SAS) AF: 0.0428 AC: 820 AN: 19158

European-Finnish (FIN) AF: 0.0910 AC: 1636 AN: 17982

Middle Eastern (MID) AF: 0.0955 AC: 47 AN: 492

European-Non Finnish (NFE) AF: 0.0642 AC: 4766 AN: 74254

Other (OTH) AF: 0.0739 AC: 489 AN: 6616

GnomAD4 genome AF: 0.102 AC: 15487 AN: 152172 Hom.: 1059 Cov.: 32 AF XY: 0.101 AC XY: 7487 AN XY: 74398

African (AFR) AF: 0.191 AC: 7905 AN: 41486

American (AMR) AF: 0.0739 AC: 1130 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3470

East Asian (EAS) AF: 0.0288 AC: 149 AN: 5182

South Asian (SAS) AF: 0.0413 AC: 199 AN: 4822

European-Finnish (FIN) AF: 0.0989 AC: 1047 AN: 10584

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4336 AN: 68024

Other (OTH) AF: 0.0953 AC: 201 AN: 2110

Alfa AF: 0.0254 Hom.: 13

Bravo AF: 0.104

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.56
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs943004; hg19: chr6-132140876;