17-79735540-C-G

Variant names:

• chr17-79735540-C-G
• rs11657217
• NM_178543.5:c.897C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178543.5(ENPP7):​c.897C>G​(p.Ala299Ala) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ENPP7	NM_178543.5	c.897C>G	p.Ala299Ala	synonymous_variant	Exon 3 of 6	ENST00000328313.10	NP_848638.3
ENPP7	XM_011524737.2	c.990C>G	p.Ala330Ala	synonymous_variant	Exon 3 of 5		XP_011523039.2
ENPP7	XR_001752505.2	n.1094C>G		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP7	ENST00000328313.10	c.897C>G	p.Ala299Ala	synonymous_variant	Exon 3 of 6	1	NM_178543.5	ENSP00000332656.5
ENPP7	ENST00000576512.1	c.-1C>G		upstream_gene_variant		2		ENSP00000460429.1

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

GnomAD2 exomes AF: 0.295 AC: 73579 AN: 249786 AF XY: 0.298

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 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

African (AFR) AF: 0.475 AC: 15886 AN: 33476

American (AMR) AF: 0.212 AC: 9498 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7458 AN: 26136

East Asian (EAS) AF: 0.159 AC: 6324 AN: 39698

South Asian (SAS) AF: 0.369 AC: 31829 AN: 86254

European-Finnish (FIN) AF: 0.309 AC: 16441 AN: 53176

Middle Eastern (MID) AF: 0.287 AC: 1658 AN: 5768

European-Non Finnish (NFE) AF: 0.308 AC: 342135 AN: 1111958

Other (OTH) AF: 0.305 AC: 18390 AN: 60388

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

African (AFR) AF: 0.466 AC: 19283 AN: 41364

American (AMR) AF: 0.250 AC: 3816 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3468

East Asian (EAS) AF: 0.106 AC: 546 AN: 5162

South Asian (SAS) AF: 0.371 AC: 1784 AN: 4810

European-Finnish (FIN) AF: 0.314 AC: 3319 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20584 AN: 67908

Other (OTH) AF: 0.311 AC: 654 AN: 2104

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
PhyloP100		0.14
PromoterAI		-0.016	Neutral
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: rs11657217; hg19: chr17-77709339;