rs1048076

Positions:

• chr6-46144635-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014936.5(ENPP4):​c.*995T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 258,144 control chromosomes in the GnomAD database, including 30,406 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 0.44 (16252 hom., cov: 32)
  • Exomes 𝑓: 0.51 (14154 hom.)
• Consequence: ENPP4 NM_014936.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP4	NM_014936.5	c.*995T>C		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.*995T>C		3_prime_UTR_variant	4/4	1	NM_014936.5	ENSP00000318066	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67129 AN: 151580 Hom.: 16250 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.505 AC: 53769 AN: 106446 Hom.: 14154 Cov.: 0 AF XY: 0.508 AC XY: 27626 AN XY: 54354

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.443 AC: 67128 AN: 151698 Hom.: 16252 Cov.: 32 AF XY: 0.447 AC XY: 33114 AN XY: 74152

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.495

Alfa AF: 0.486 Hom.: 6058

Bravo AF: 0.426

Asia WGS AF: 0.539 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.61

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: rs1048076; hg19: chr6-46112372;