chr6-131882330-AT-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006208.3(ENPP1):c.2101-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 16487 hom., cov: 0)

Exomes 𝑓: 0.25 ( 52704 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:2

Conservation

PhyloP100: 0.184

Publications

15 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 Gene-Disease associations (from GenCC):

arterial calcification, generalized, of infancy, 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
hypopigmentation-punctate palmoplantar keratoderma syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
hypophosphatemic rickets, autosomal recessive, 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arterial calcification of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive hypophosphatemic rickets
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive inherited pseudoxanthoma elasticum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENPP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 6-131882330-AT-A is Benign according to our data. Variant chr6-131882330-AT-A is described in ClinVar as Benign. ClinVar VariationId is 355347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP1	NM_006208.3 link	c.2101-11delT		intron_variant	Intron 20 of 24	ENST00000647893.1	NP_006199.2	P22413

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENPP1	ENST00000647893.1 link	c.2101-14delT	intron_variant	Intron 20 of 24		NM_006208.3	ENSP00000498074.1	P22413
ENPP1	ENST00000513998.5 link	n.*938-14delT	intron_variant	Intron 20 of 24	5		ENSP00000422424.1	E9PE72
ENPP1	ENST00000684674.1 link	n.532-14delT	intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60281

AN:

150348

Hom.:

16444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.407

GnomAD2 exomes

AF:

0.319

AC:

80052

AN:

250838

AF XY:

0.308

show subpopulations

Gnomad AFR exome

AF:

0.774

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.247

AC:

355027

AN:

1438970

Hom.:

52704

Cov.:

AF XY:

0.248

AC XY:

178024

AN XY:

716614

show subpopulations

African (AFR)

AF:

0.790

AC:

25803

AN:

32682

American (AMR)

AF:

0.459

AC:

20282

AN:

44174

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

8573

AN:

25188

East Asian (EAS)

AF:

0.330

AC:

12618

AN:

38234

South Asian (SAS)

AF:

0.370

AC:

31781

AN:

85894

European-Finnish (FIN)

AF:

0.210

AC:

10904

AN:

51930

Middle Eastern (MID)

AF:

0.400

AC:

2257

AN:

5648

European-Non Finnish (NFE)

AF:

0.206

AC:

225626

AN:

1096382

Other (OTH)

AF:

0.292

AC:

17183

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10327

20653

30980

41306

51633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8348

16696

25044

33392

41740

<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:

0.401

AC:

60379

AN:

150456

Hom.:

16487

Cov.:

AF XY:

0.402

AC XY:

29571

AN XY:

73516

show subpopulations

African (AFR)

AF:

0.768

AC:

31634

AN:

41204

American (AMR)

AF:

0.436

AC:

6584

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1194

AN:

3456

East Asian (EAS)

AF:

0.320

AC:

1635

AN:

5106

South Asian (SAS)

AF:

0.379

AC:

1821

AN:

4802

European-Finnish (FIN)

AF:

0.202

AC:

1991

AN:

9848

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.211

AC:

14285

AN:

67660

Other (OTH)

AF:

0.406

AC:

845

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1375

2750

4126

5501

6876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.308

Hom.:

1758

Bravo

AF:

0.433

Asia WGS

AF:

0.387

AC:

1345

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Arterial calcification, generalized, of infancy, 1

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 09, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.2101-11delT in intron 20 of ENPP1: This variant is not expected to have clinic al significance because it has been identified in 85.70% (1133/1322) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs1799774). -

Hypophosphatemic Rickets, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypophosphatemic rickets, autosomal recessive, 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypopigmentation-punctate palmoplantar keratoderma syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diabetes mellitus type 2, susceptibility to

Other:1

Jul 01, 2006

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Obesity

Other:1

Jul 01, 2006

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over