rs1510

Variant names:

• chr6-131893782-C-G
• rs1510
• NM_006208.3:c.*3271C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-131893782-C-G
• chr6-131893782-C-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.*3271C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 151,750 control chromosomes in the GnomAD database, including 1,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (1060 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENPP1 NM_006208.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.298
• 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, ClinGen
• hypopigmentation-punctate palmoplantar keratoderma syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.82).
• BP6: Variant 6-131893782-C-G is Benign according to our data. Variant chr6-131893782-C-G is described in ClinVar as Benign. ClinVar VariationId is 355415.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	NM_006208.3	MANE Select	c.*3271C>G		3_prime_UTR	Exon 25 of 25	NP_006199.2	P22413

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	ENST00000647893.1	MANE Select	c.*3271C>G		3_prime_UTR	Exon 25 of 25	ENSP00000498074.1	P22413
	ENPP1	ENST00000922186.1		c.*3271C>G		3_prime_UTR	Exon 24 of 24	ENSP00000592245.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14745 AN: 151630 Hom.: 1062 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0886

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0972 AC: 14744 AN: 151746 Hom.: 1060 Cov.: 32 AF XY: 0.102 AC XY: 7546 AN XY: 74126

African (AFR) AF: 0.0202 AC: 838 AN: 41448

American (AMR) AF: 0.0673 AC: 1025 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 311 AN: 3464

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5160

South Asian (SAS) AF: 0.0776 AC: 372 AN: 4792

European-Finnish (FIN) AF: 0.271 AC: 2822 AN: 10418

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9013 AN: 67916

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

Alfa AF: 0.123 Hom.: 184

Bravo AF: 0.0771

Asia WGS AF: 0.0370 AC: 128 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Arterial calcification, generalized, of infancy, 1 (1)
-	-	1	Hypophosphatemic rickets, autosomal recessive, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
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: rs1510; hg19: chr6-132214922;