17-79735540-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178543.5(ENPP7):c.897C>G(p.Ala299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,432 control chromosomes in the GnomAD database, including 80,560 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 0.34 (9387 hom., cov: 31)
  • Exomes 𝑓: 0.31 (71173 hom.)
• Consequence: ENPP7 NM_178543.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

Genes affected

ENPP7 (HGNC:23764): (ectonucleotide pyrophosphatase/phosphodiesterase 7) The protein encoded by this gene is an intestinal alkaline sphingomyelin phosphodiesterase that converts sphingomyelin to ceramide and phosphocholine. The encoded protein is anchored in the cell membrane, and it may function to protect the intestinal mucosa from inflammation and tumorigenesis. This protein is glycosylated and also exhibits lysophosphatidylcholine hydrolase activity. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.142 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP7	NM_178543.5	c.897C>G	p.Ala299=	synonymous_variant	3/6	ENST00000328313.10
ENPP7	XM_011524737.2	c.990C>G	p.Ala330=	synonymous_variant	3/5
ENPP7	XR_001752505.2	n.1094C>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP7	ENST00000328313.10	c.897C>G	p.Ala299=	synonymous_variant	3/6	1	NM_178543.5	P1
ENPP7	ENST00000576512.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51333 AN: 151742 Hom.: 9376 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.311

GnomAD3 exomes AF: 0.295 AC: 73579 AN: 249786 Hom.: 11791 AF XY: 0.298 AC XY: 40305 AN XY: 135200

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.0986

Gnomad SAS exome AF: 0.371

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.308 AC: 449619 AN: 1461570 Hom.: 71173 Cov.: 53 AF XY: 0.309 AC XY: 224631 AN XY: 727108

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.338 AC: 51388 AN: 151862 Hom.: 9387 Cov.: 31 AF XY: 0.337 AC XY: 25004 AN XY: 74236

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.311

Alfa AF: 0.257 Hom.: 1713

Bravo AF: 0.335

Asia WGS AF: 0.270 AC: 942 AN: 3478

EpiCase AF: 0.296

EpiControl AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.3
Dann	Benign	0.41

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: rs11657217; hg19: chr17-77709339;