rs1048077

Variant names:

• chr6-46144652-A-G
• rs1048077
• NM_014936.5:c.*1012A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014936.5(ENPP4):​c.*1012A>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 0.733 in 291,760 control chromosomes in the GnomAD database, including 79,812 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 0.76 (44873 hom., cov: 33)
  • Exomes 𝑓: 0.70 (34939 hom.)
• Consequence: ENPP4 NM_014936.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.59
• Publications: 9 publications found

Genes affected

ENPP4 (HGNC:3359): (ectonucleotide pyrophosphatase/phosphodiesterase 4) Enables bis(5'-adenosyl)-triphosphatase activity. Involved in positive regulation of blood coagulation and purine ribonucleoside catabolic process. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP4	NM_014936.5	MANE Select	c.*1012A>G		3_prime_UTR	Exon 4 of 4	NP_055751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP4	ENST00000321037.5	TSL:1 MANE Select	c.*1012A>G		3_prime_UTR	Exon 4 of 4	ENSP00000318066.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115428 AN: 151750 Hom.: 44808 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.703 AC: 98344 AN: 139892 Hom.: 34939 Cov.: 0 AF XY: 0.702 AC XY: 50220 AN XY: 71556

African (AFR) AF: 0.921 AC: 4449 AN: 4828

American (AMR) AF: 0.767 AC: 3378 AN: 4404

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 4343 AN: 5640

East Asian (EAS) AF: 0.766 AC: 9780 AN: 12766

South Asian (SAS) AF: 0.798 AC: 1026 AN: 1286

European-Finnish (FIN) AF: 0.733 AC: 6305 AN: 8602

Middle Eastern (MID) AF: 0.846 AC: 665 AN: 786

European-Non Finnish (NFE) AF: 0.667 AC: 61331 AN: 91900

Other (OTH) AF: 0.730 AC: 7067 AN: 9680

GnomAD4 genome AF: 0.761 AC: 115549 AN: 151868 Hom.: 44873 Cov.: 33 AF XY: 0.767 AC XY: 56940 AN XY: 74246

African (AFR) AF: 0.921 AC: 38216 AN: 41484

American (AMR) AF: 0.769 AC: 11688 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2682 AN: 3466

East Asian (EAS) AF: 0.832 AC: 4308 AN: 5176

South Asian (SAS) AF: 0.790 AC: 3812 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7779 AN: 10594

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44577 AN: 67820

Other (OTH) AF: 0.768 AC: 1620 AN: 2110

Alfa AF: 0.736 Hom.: 15888

Bravo AF: 0.771

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.034
DANN	Benign	0.50
PhyloP100		-3.6
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: rs1048077; hg19: chr6-46112389; COSMIC: COSV58088903;