chr6-131847857-G-T

Position:

chr6-131847857-G-T

Variant summary

Our verdict is Benign. Variant got -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

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:

ENPP1 (HGNC:):

ENPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3 linkuse as main transcript	c.313+9G>T		intron_variant		ENST00000647893.1	NP_006199.2	P22413

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ENPP1	ENST00000647893.1 linkuse as main transcript	c.313+9G>T	intron_variant		NM_006208.3	ENSP00000498074.1	P22413
ENPP1	ENST00000486853.1 linkuse as main transcript	n.333+9G>T	intron_variant	2
ENPP1	ENST00000513998.5 linkuse as main transcript	n.313+9G>T	intron_variant	5		ENSP00000422424.1	E9PE72
ENPP1	ENST00000650507.1 linkuse as main transcript	n.*149+9G>T	intron_variant			ENSP00000497375.1	A0A3B3IST7

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

GnomAD3 exomes

AF:

0.0531

AC:

5932

AN:

111610

Hom.:

215

AF XY:

0.0518

AC XY:

3103

AN XY:

59928

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 SAS exome

AF:

0.0415

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

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0218

Gnomad4 ASJ exome

AF:

0.0523

Gnomad4 EAS exome

AF:

0.000867

Gnomad4 SAS exome

AF:

0.0582

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0830

Gnomad4 OTH exome

AF:

0.0836

GnomAD4 genome

AF:

0.109

AC:

3850

AN:

35196

Hom.:

Cov.:

AF XY:

0.110

AC XY:

1807

AN XY:

16456

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0606

Gnomad4 ASJ

AF:

0.0618

Gnomad4 EAS

AF:

0.000861

Gnomad4 SAS

AF:

0.0813

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.0794

Gnomad4 OTH

AF:

0.0923

Alfa

AF:

0.0516

Hom.:

241

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2019	- -

Hypophosphatemic rickets, autosomal recessive, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Arterial calcification, generalized, of infancy, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.75

DANN

Benign

0.44

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