rs7773477

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006208.3(ENPP1):c.313+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 61 hom., cov: 0)

Exomes 𝑓: 0.082 ( 325 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.525

Publications

5 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, ClinGen
hypopigmentation-punctate palmoplantar keratoderma syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-131847857-G-T is Benign according to our data. Variant chr6-131847857-G-T is described in ClinVar as Benign. ClinVar VariationId is 355335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.313+9G>T		intron	N/A	NP_006199.2	P22413

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENPP1	ENST00000647893.1	MANE Select	c.313+9G>T	intron	N/A	ENSP00000498074.1	P22413
ENPP1	ENST00000922186.1		c.313+9G>T	intron	N/A	ENSP00000592245.1
ENPP1	ENST00000486853.1	TSL:2	n.333+9G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

3847

AN:

35208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0618

Gnomad EAS

AF:

0.000856

Gnomad SAS

AF:

0.0806

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0375

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.0934

GnomAD2 exomes

AF:

0.0531

AC:

5932

AN:

111610

AF XY:

0.0518

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.00374

Gnomad FIN exome

AF:

0.0876

Gnomad NFE exome

AF:

0.0567

Gnomad OTH exome

AF:

0.0449

GnomAD4 exome

AF:

0.0817

AC:

26789

AN:

327864

Hom.:

325

Cov.:

AF XY:

0.0775

AC XY:

12836

AN XY:

165614

show subpopulations

African (AFR)

AF:

0.233

AC:

1864

AN:

7996

American (AMR)

AF:

0.0218

AC:

240

AN:

11022

Ashkenazi Jewish (ASJ)

AF:

0.0523

AC:

384

AN:

7338

East Asian (EAS)

AF:

0.000867

AC:

AN:

6924

South Asian (SAS)

AF:

0.0582

AC:

1185

AN:

20350

European-Finnish (FIN)

AF:

0.125

AC:

978

AN:

7850

Middle Eastern (MID)

AF:

0.0993

AC:

107

AN:

1078

European-Non Finnish (NFE)

AF:

0.0830

AC:

20913

AN:

252012

Other (OTH)

AF:

0.0836

AC:

1112

AN:

13294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

775

1551

2326

3102

3877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.109

AC:

3850

AN:

35196

Hom.:

Cov.:

AF XY:

0.110

AC XY:

1807

AN XY:

16456

show subpopulations

African (AFR)

AF:

0.183

AC:

1875

AN:

10246

American (AMR)

AF:

0.0606

AC:

180

AN:

2968

Ashkenazi Jewish (ASJ)

AF:

0.0618

AC:

AN:

874

East Asian (EAS)

AF:

0.000861

AC:

AN:

1162

South Asian (SAS)

AF:

0.0813

AC:

AN:

800

European-Finnish (FIN)

AF:

0.181

AC:

266

AN:

1466

Middle Eastern (MID)

AF:

0.0405

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0794

AC:

1345

AN:

16940

Other (OTH)

AF:

0.0923

AC:

AN:

520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

186

372

558

744

930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0555

Hom.:

327

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Arterial calcification, generalized, of infancy, 1 (1)

Hypophosphatemic rickets, autosomal recessive, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.75

(source)

DANN

Benign

0.44

PhyloP100

-0.53

Mutation Taster

=13/87

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over