rs7768480

Variant names:

• chr6-131882292-A-G
• rs7768480
• NM_006208.3:c.2101-53A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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
• hypopigmentation-punctate palmoplantar keratoderma syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ENPP1	NM_006208.3	c.2101-53A>G		intron_variant	Intron 20 of 24	ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP1	ENST00000647893.1	c.2101-53A>G		intron_variant	Intron 20 of 24		NM_006208.3	ENSP00000498074.1
ENPP1	ENST00000513998.5	n.*938-53A>G		intron_variant	Intron 20 of 24	5		ENSP00000422424.1
ENPP1	ENST00000684674.1	n.532-53A>G		intron_variant	Intron 1 of 5

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

African (AFR) AF: 0.486 AC: 14914 AN: 30664

American (AMR) AF: 0.196 AC: 8541 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3706 AN: 24072

East Asian (EAS) AF: 0.143 AC: 5227 AN: 36634

South Asian (SAS) AF: 0.119 AC: 10084 AN: 84784

European-Finnish (FIN) AF: 0.0502 AC: 2498 AN: 49738

Middle Eastern (MID) AF: 0.137 AC: 747 AN: 5462

European-Non Finnish (NFE) AF: 0.0777 AC: 81635 AN: 1050882

Other (OTH) AF: 0.122 AC: 6830 AN: 56194

GnomAD4 genome AF: 0.205 AC: 30873 AN: 150520 Hom.: 5428 Cov.: 31 AF XY: 0.201 AC XY: 14764 AN XY: 73508

African (AFR) AF: 0.478 AC: 19648 AN: 41146

American (AMR) AF: 0.191 AC: 2878 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3462

East Asian (EAS) AF: 0.144 AC: 741 AN: 5144

South Asian (SAS) AF: 0.123 AC: 587 AN: 4782

European-Finnish (FIN) AF: 0.0395 AC: 391 AN: 9910

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.0799 AC: 5409 AN: 67716

Other (OTH) AF: 0.204 AC: 426 AN: 2086

Alfa AF: 0.113 Hom.: 1822

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

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.50
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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