rs2295017

chr6-46160099-T-A

Variant summary

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

The NM_001290072.2(ENPP5):c.*1227A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,110 control chromosomes in the GnomAD database, including 7,704 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 0.31 (7704 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENPP5 NM_001290072.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

ENPP5 (HGNC:13717): (ectonucleotide pyrophosphatase/phosphodiesterase family member 5) This gene encodes a type-I transmembrane glycoprotein. Studies in rat suggest the encoded protein may play a role in neuronal cell communications. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP5	NM_001290072.2	c.*1227A>T		3_prime_UTR_variant	5/5	ENST00000371383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP5	ENST00000371383.7	c.*1227A>T		3_prime_UTR_variant	5/5	1	NM_001290072.2	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46806 AN: 151992 Hom.: 7711 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.308 AC: 46807 AN: 152110 Hom.: 7704 Cov.: 32 AF XY: 0.308 AC XY: 22917 AN XY: 74360

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.348

Alfa AF: 0.332 Hom.: 1161

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.5
Dann	Benign	0.68

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: rs2295017; hg19: chr6-46127836;