Genetic Variant ENPP1:c.240+11597C>T (chr6-131819872-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+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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0670

Publications

9 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:

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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=-0.87).

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 rank	MANE	Protein	UniProt
ENPP1	NM_006208.3 link	c.240+11597C>T		intron_variant	Intron 1 of 24	ENST00000647893.1	NP_006199.2	P22413
SELENOKP2		n.131819872C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1 link	c.240+11597C>T		intron_variant	Intron 1 of 24		NM_006208.3	ENSP00000498074.1		P22413

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98061

AN:

151756

Hom.:

32194

Cov.:

show subpopulations

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.:

AF XY:

0.622

AC XY:

108759

AN XY:

174994

show subpopulations

African (AFR)

AF:

0.720

AC:

5217

AN:

7248

American (AMR)

AF:

0.522

AC:

8993

AN:

17244

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

6001

AN:

9002

East Asian (EAS)

AF:

0.824

AC:

10799

AN:

13110

South Asian (SAS)

AF:

0.661

AC:

31563

AN:

47720

European-Finnish (FIN)

AF:

0.574

AC:

15995

AN:

27858

Middle Eastern (MID)

AF:

0.693

AC:

1252

AN:

1806

European-Non Finnish (NFE)

AF:

0.598

AC:

102959

AN:

172198

Other (OTH)

AF:

0.618

AC:

9464

AN:

15302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3247

6494

9741

12988

16235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.646

AC:

98124

AN:

151870

Hom.:

32212

Cov.:

AF XY:

0.645

AC XY:

47891

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.721

AC:

29872

AN:

41426

American (AMR)

AF:

0.593

AC:

9042

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2360

AN:

3462

East Asian (EAS)

AF:

0.821

AC:

4242

AN:

5168

South Asian (SAS)

AF:

0.679

AC:

3271

AN:

4814

European-Finnish (FIN)

AF:

0.578

AC:

6073

AN:

10498

Middle Eastern (MID)

AF:

0.712

AC:

208

AN:

292

European-Non Finnish (NFE)

AF:

0.608

AC:

41276

AN:

67936

Other (OTH)

AF:

0.667

AC:

1408

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1720

3440

5159

6879

8599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.531

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

(source)

DANN

Benign

0.59

PhyloP100

-0.067

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

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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