rs7768480

Positions:

• chr6-131882292-A-G
• chr6-131882292-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

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]

ACMG classification

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	UniProt
ENPP1	NM_006208.3	c.2101-53A>G		intron_variant		ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP1	ENST00000647893.1	c.2101-53A>G		intron_variant			NM_006208.3	P1
ENPP1	ENST00000513998.5	c.*938-53A>G		intron_variant, NMD_transcript_variant		5
ENPP1	ENST00000684674.1	n.532-53A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30819 AN: 150416 Hom.: 5415 Cov.: 31

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

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.: 31 AF XY: 0.201 AC XY: 14764 AN XY: 73508

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

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

Other links and lift over

dbSNP: rs7768480; hg19: chr6-132203432; COSMIC: COSV62931092; COSMIC: COSV62931092;