rs1048077

Positions:

• chr6-46144652-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP4	NM_014936.5	c.*1012A>G		3_prime_UTR_variant	4/4	ENST00000321037.5	NP_055751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP4	ENST00000321037.5	c.*1012A>G		3_prime_UTR_variant	4/4	1	NM_014936.5	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

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.770

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.798

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.730

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

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.768

Alfa AF: 0.742 Hom.: 8927

Bravo AF: 0.771

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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