chr6-131853789-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006208.3(ENPP1):​c.618-1137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,982 control chromosomes in the GnomAD database, including 11,982 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 11982 hom., cov: 32)

Consequence

ENPP1
NM_006208.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENPP1NM_006208.3 linkuse as main transcriptc.618-1137G>C intron_variant ENST00000647893.1 NP_006199.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENPP1ENST00000647893.1 linkuse as main transcriptc.618-1137G>C intron_variant NM_006208.3 ENSP00000498074 P1
ENPP1ENST00000513998.5 linkuse as main transcriptc.618-1137G>C intron_variant, NMD_transcript_variant 5 ENSP00000422424
ENPP1ENST00000650147.1 linkuse as main transcriptc.235-1137G>C intron_variant, NMD_transcript_variant ENSP00000497519
ENPP1ENST00000650437.1 linkuse as main transcriptc.109-1137G>C intron_variant, NMD_transcript_variant ENSP00000497981

Frequencies

GnomAD3 genomes
AF:
0.307
AC:
46681
AN:
151864
Hom.:
11930
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.706
Gnomad AMI
AF:
0.316
Gnomad AMR
AF:
0.239
Gnomad ASJ
AF:
0.231
Gnomad EAS
AF:
0.0933
Gnomad SAS
AF:
0.145
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.142
Gnomad OTH
AF:
0.281
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.308
AC:
46794
AN:
151982
Hom.:
11982
Cov.:
32
AF XY:
0.302
AC XY:
22425
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.707
Gnomad4 AMR
AF:
0.238
Gnomad4 ASJ
AF:
0.231
Gnomad4 EAS
AF:
0.0931
Gnomad4 SAS
AF:
0.146
Gnomad4 FIN
AF:
0.123
Gnomad4 NFE
AF:
0.142
Gnomad4 OTH
AF:
0.282
Alfa
AF:
0.231
Hom.:
955
Bravo
AF:
0.334
Asia WGS
AF:
0.151
AC:
529
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.030
DANN
Benign
0.41

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.

Other links and lift over

dbSNP: rs7767502; hg19: chr6-132174929; API