rs2074932

Positions:

• chr14-73974981-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001249.5(ENTPD5):​c.727C>T​(p.Leu243Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,608,022 control chromosomes in the GnomAD database, including 308,026 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 0.55 (24522 hom., cov: 31)
  • Exomes 𝑓: 0.62 (283504 hom.)
• Consequence: ENTPD5 NM_001249.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

ENTPD5 (HGNC:3367): (ectonucleoside triphosphate diphosphohydrolase 5 (inactive)) The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD5	NM_001249.5	c.727C>T	p.Leu243Leu	synonymous_variant	11/16	ENST00000334696.11	NP_001240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD5	ENST00000334696.11	c.727C>T	p.Leu243Leu	synonymous_variant	11/16	5	NM_001249.5	ENSP00000335246.6
ENTPD5	ENST00000557325.5	c.727C>T	p.Leu243Leu	synonymous_variant	11/16	2		ENSP00000451810.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84256 AN: 151802 Hom.: 24521 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.568

GnomAD3 exomes AF: 0.600 AC: 150426 AN: 250886 Hom.: 47253 AF XY: 0.603 AC XY: 81779 AN XY: 135604

Gnomad AFR exome AF: 0.393

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.620

Gnomad FIN exome AF: 0.688

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.623

GnomAD4 exome AF: 0.619 AC: 901209 AN: 1456102 Hom.: 283504 Cov.: 33 AF XY: 0.619 AC XY: 448592 AN XY: 724704

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.555 AC: 84277 AN: 151920 Hom.: 24522 Cov.: 31 AF XY: 0.557 AC XY: 41358 AN XY: 74256

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.567

Alfa AF: 0.612 Hom.: 65336

Bravo AF: 0.544

Asia WGS AF: 0.469 AC: 1634 AN: 3476

EpiCase AF: 0.621

EpiControl AF: 0.629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.7
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2074932; hg19: chr14-74441684; COSMIC: COSV58221894; COSMIC: COSV58221894;