10-95756154-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000453258.6(ENTPD1):c.37+44161A>C variant causes a intron change. The variant allele was found at a frequency of 0.00164 in 1,556,112 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (18 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (46 hom.)
• Consequence: ENTPD1 ENST00000453258.6 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

Genes affected

ENTPD1 (HGNC:3363): (ectonucleoside triphosphate diphosphohydrolase 1) The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTPD1-AS1	NR_038444.1	n.1314T>G		non_coding_transcript_exon_variant	6/6
ENTPD1	NM_001776.6			upstream_gene_variant		ENST00000371205.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTPD1-AS1	ENST00000669711.1	n.849-290T>G		intron_variant, non_coding_transcript_variant
ENTPD1	ENST00000371205.5			upstream_gene_variant		1	NM_001776.6	P1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 381 AN: 151668 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0000970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.00499

Gnomad FIN AF: 0.0000950

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.00155 AC: 2177 AN: 1404326 Hom.: 46 Cov.: 31 AF XY: 0.00159 AC XY: 1104 AN XY: 693468

Gnomad4 AFR exome AF: 0.0000631

Gnomad4 AMR exome AF: 0.000304

Gnomad4 ASJ exome AF: 0.000238

Gnomad4 EAS exome AF: 0.0452

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.000160

Gnomad4 NFE exome AF: 0.0000453

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.00251 AC: 381 AN: 151786 Hom.: 18 Cov.: 31 AF XY: 0.00280 AC XY: 208 AN XY: 74176

Gnomad4 AFR AF: 0.0000967

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.00500

Gnomad4 FIN AF: 0.0000950

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000738 Hom.: 1

Bravo AF: 0.00275

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 22, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	19
Dann	Benign	0.94

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: rs75902129; hg19: chr10-97515911;