Genetic Variant ENPP1:c.240+11461C>T (chr6-131819736-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.358

Publications

2 publications found

Variant links:

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]

ENPP1 links:

SELENOKP2 (HGNC:53725): (selenoprotein K pseudogene 2)

SELENOKP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP1	NM_006208.3 link	c.240+11461C>T		intron_variant	Intron 1 of 24	ENST00000647893.1	NP_006199.2
SELENOKP2		n.131819736C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1 link	c.240+11461C>T		intron_variant	Intron 1 of 24		NM_006208.3	ENSP00000498074.1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15469

AN:

152056

Hom.:

1055

Cov.:

show subpopulations

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

show subpopulations

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:

AN:

492

European-Non Finnish (NFE)

AF:

0.0642

AC:

4766

AN:

74254

Other (OTH)

AF:

0.0739

AC:

489

AN:

6616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

367

733

1100

1466

1833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.102

AC:

15487

AN:

152172

Hom.:

1059

Cov.:

AF XY:

0.101

AC XY:

7487

AN XY:

74398

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4336

AN:

68024

Other (OTH)

AF:

0.0953

AC:

201

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

679

1358

2036

2715

3394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.104

Asia WGS

AF:

0.0350

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.8

(source)

DANN

Benign

0.56

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over