chr14-73974981-G-A

Variant names:

• chr14-73974981-G-A
• rs2074932
• NM_001249.5:c.727C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	NM_001249.5	MANE Select	c.727C>T	p.Leu243Leu	synonymous	Exon 11 of 16	NP_001240.1	O75356
	ENTPD5	NM_001321985.3		c.727C>T	p.Leu243Leu	synonymous	Exon 12 of 17	NP_001308914.1	O75356
	ENTPD5	NM_001321986.3		c.727C>T	p.Leu243Leu	synonymous	Exon 12 of 17	NP_001308915.1	O75356

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD5	ENST00000334696.11	TSL:5 MANE Select	c.727C>T	p.Leu243Leu	synonymous	Exon 11 of 16	ENSP00000335246.6	O75356
	ENTPD5	ENST00000900912.1		c.751C>T	p.Leu251Leu	synonymous	Exon 9 of 14	ENSP00000570971.1
	ENTPD5	ENST00000900901.1		c.736C>T	p.Leu246Leu	synonymous	Exon 10 of 15	ENSP00000570960.1

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

GnomAD2 exomes AF: 0.600 AC: 150426 AN: 250886 AF XY: 0.603

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 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

African (AFR) AF: 0.382 AC: 12755 AN: 33356

American (AMR) AF: 0.707 AC: 31545 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 16395 AN: 26076

East Asian (EAS) AF: 0.299 AC: 11845 AN: 39662

South Asian (SAS) AF: 0.619 AC: 53294 AN: 86048

European-Finnish (FIN) AF: 0.689 AC: 36784 AN: 53392

Middle Eastern (MID) AF: 0.578 AC: 3326 AN: 5754

European-Non Finnish (NFE) AF: 0.631 AC: 698957 AN: 1106982

Other (OTH) AF: 0.603 AC: 36308 AN: 60214

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

African (AFR) AF: 0.396 AC: 16415 AN: 41406

American (AMR) AF: 0.647 AC: 9868 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5172

South Asian (SAS) AF: 0.609 AC: 2936 AN: 4818

European-Finnish (FIN) AF: 0.693 AC: 7311 AN: 10548

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42320 AN: 67944

Other (OTH) AF: 0.567 AC: 1196 AN: 2108

Alfa AF: 0.603 Hom.: 88333

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs2074932; hg19: chr14-74441684; COSMIC: COSV58221894; COSMIC: COSV58221894;