rs11752816

Positions:

• chr6-46139575-G-A
• chr6-46139575-G-C
• chr6-46139575-G-T

Variant summary

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

The NM_014936.5(ENPP4):​c.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,345,790 control chromosomes in the GnomAD database, including 20,705 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 0.13 (1793 hom., cov: 31)
  • Exomes 𝑓: 0.17 (18912 hom.)
• Consequence: ENPP4 NM_014936.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP4	NM_014936.5	c.-9G>A		5_prime_UTR_variant	2/4	ENST00000321037.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP4	ENST00000321037.5	c.-9G>A		5_prime_UTR_variant	2/4	1	NM_014936.5	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20096 AN: 151322 Hom.: 1793 Cov.: 31

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.173 AC: 42264 AN: 244884 Hom.: 4467 AF XY: 0.182 AC XY: 24138 AN XY: 132308

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.0986

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.274

Gnomad SAS exome AF: 0.323

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.168 AC: 200327 AN: 1194348 Hom.: 18912 Cov.: 16 AF XY: 0.174 AC XY: 105463 AN XY: 607622

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.133 AC: 20097 AN: 151442 Hom.: 1793 Cov.: 31 AF XY: 0.136 AC XY: 10083 AN XY: 73986

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.148

Alfa AF: 0.156 Hom.: 3913

Bravo AF: 0.122

Asia WGS AF: 0.305 AC: 1059 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11752816; hg19: chr6-46107312; COSMIC: COSV58089052;