10-95823211-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001776.6(ENTPD1):c.17-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,612,854 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (27 hom., cov: 33)
  • Exomes 𝑓: 0.019 (375 hom.)
• Consequence: ENTPD1 NM_001776.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-95823211-T-C is Benign according to our data. Variant chr10-95823211-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1342044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0145 (2207/152364) while in subpopulation SAS AF= 0.0213 (103/4830). AF 95% confidence interval is 0.0199. There are 27 homozygotes in gnomad4. There are 1068 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTPD1	NM_001776.6	c.17-26T>C		intron_variant		ENST00000371205.5
ENTPD1-AS1	NR_038444.1	n.533+24181A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTPD1	ENST00000371205.5	c.17-26T>C		intron_variant		1	NM_001776.6	P1
ENTPD1-AS1	ENST00000669711.1	n.444-37966A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2205 AN: 152246 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0150 AC: 3762 AN: 251332 Hom.: 51 AF XY: 0.0157 AC XY: 2135 AN XY: 135866

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0174

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0195

Gnomad OTH exome AF: 0.0129

GnomAD4 exome AF: 0.0194 AC: 28291 AN: 1460490 Hom.: 375 Cov.: 31 AF XY: 0.0193 AC XY: 14031 AN XY: 726548

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.00584

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0212

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0145 AC: 2207 AN: 152364 Hom.: 27 Cov.: 33 AF XY: 0.0143 AC XY: 1068 AN XY: 74504

Gnomad4 AFR AF: 0.00315

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0213

Gnomad4 FIN AF: 0.0233

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0187 Hom.: 6

Bravo AF: 0.0127

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	12
Dann	Benign	0.84

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: rs3176889; hg19: chr10-97582968;