rs1048076

Variant names:

• chr6-46144635-T-C
• rs1048076
• NM_014936.5:c.*995T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.83).
• 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 rank	MANE	Protein	UniProt
ENPP4	NM_014936.5	c.*995T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000321037.5	NP_055751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP4	ENST00000321037.5	c.*995T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_014936.5	ENSP00000318066.3

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

African (AFR) AF: 0.234 AC: 946 AN: 4050

American (AMR) AF: 0.438 AC: 1459 AN: 3332

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2692 AN: 4488

East Asian (EAS) AF: 0.367 AC: 3489 AN: 9516

South Asian (SAS) AF: 0.673 AC: 653 AN: 970

European-Finnish (FIN) AF: 0.508 AC: 2980 AN: 5868

Middle Eastern (MID) AF: 0.660 AC: 396 AN: 600

European-Non Finnish (NFE) AF: 0.533 AC: 37375 AN: 70104

Other (OTH) AF: 0.503 AC: 3779 AN: 7518

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

African (AFR) AF: 0.235 AC: 9747 AN: 41438

American (AMR) AF: 0.459 AC: 6970 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2085 AN: 3464

East Asian (EAS) AF: 0.433 AC: 2236 AN: 5164

South Asian (SAS) AF: 0.672 AC: 3236 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5235 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35829 AN: 67756

Other (OTH) AF: 0.495 AC: 1045 AN: 2110

Alfa AF: 0.484 Hom.: 7521

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
PhyloP100		-0.23
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: rs1048076; hg19: chr6-46112372;