rs1799774

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006208.3(ENPP1):c.2101-11del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.184

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 355347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-131882330-AT-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3 linkuse as main transcript	c.2101-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ENPP1	ENST00000647893.1 linkuse as main transcript	c.2101-11del	splice_polypyrimidine_tract_variant, intron_variant		NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5 linkuse as main transcript	c.*938-11del	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5		ENSP00000422424
ENPP1	ENST00000684674.1 linkuse as main transcript	n.532-11del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.319

AC:

80052

AN:

250838

Hom.:

15795

AF XY:

0.308

AC XY:

41753

AN XY:

135610

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 SAS exome

AF:

0.370

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

Gnomad4 AFR exome

AF:

0.790

Gnomad4 AMR exome

AF:

0.459

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.401

AC:

60379

AN:

150456

Hom.:

16487

Cov.:

AF XY:

0.402

AC XY:

29571

AN XY:

73516

show subpopulations

Gnomad4 AFR

AF:

0.768

Gnomad4 AMR

AF:

0.436

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.406

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 09, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypophosphatemic rickets, autosomal recessive, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Hypopigmentation-punctate palmoplantar keratoderma syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Diabetes mellitus type 2, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2006

- -

Obesity

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over