Variant rs7768480 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006208.3(ENPP1):c.2101-53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,532,622 control chromosomes in the GnomAD database, including 15,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 5428 hom., cov: 31)

Exomes 𝑓: 0.097 ( 9831 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.46

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-131882292-A-G is Benign according to our data. Variant chr6-131882292-A-G is described in ClinVar as [Benign]. Clinvar id is 1230336.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 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.2101-53A>G		intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ENPP1	ENST00000647893.1 linkuse as main transcript	c.2101-53A>G	intron_variant		NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5 linkuse as main transcript	c.*938-53A>G	intron_variant, NMD_transcript_variant	5		ENSP00000422424
ENPP1	ENST00000684674.1 linkuse as main transcript	n.532-53A>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

30819

AN:

150416

Hom.:

5415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0799

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.0971

AC:

134182

AN:

1382102

Hom.:

9831

AF XY:

0.0963

AC XY:

66623

AN XY:

691742

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0502

Gnomad4 NFE exome

AF:

0.0777

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.205

AC:

30873

AN:

150520

Hom.:

5428

Cov.:

AF XY:

0.201

AC XY:

14764

AN XY:

73508

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0799

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.107

Hom.:

1371

Bravo

AF:

0.230

Asia WGS

AF:

0.132

AC:

459

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.010

DANN

Benign

0.50

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

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