rs3176892

Variant names:

• chr10-95755831-T-C
• rs3176892
• ENST00000453258.6:c.37+43838T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001164178.1(ENTPD1):​c.52+65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,511,276 control chromosomes in the GnomAD database, including 1,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (119 hom., cov: 31)
  • Exomes 𝑓: 0.043 (1421 hom.)
• Consequence: ENTPD1 NM_001164178.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.192

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-95755831-T-C is Benign according to our data. Variant chr10-95755831-T-C is described in ClinVar as [Benign]. Clinvar id is 1234750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0338 (5131/151994) while in subpopulation NFE AF= 0.0494 (3356/67976). AF 95% confidence interval is 0.048. There are 119 homozygotes in gnomad4. There are 2470 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 119 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD1	NM_001164178.1	c.52+65T>C		intron_variant	Intron 1 of 9		NP_001157650.1
ENTPD1	NM_001098175.2	c.37+43838T>C		intron_variant	Intron 1 of 9		NP_001091645.1
ENTPD1	NM_001320916.1	c.52+65T>C		intron_variant	Intron 1 of 9		NP_001307845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD1	ENST00000453258.6	c.37+43838T>C		intron_variant	Intron 1 of 9	1		ENSP00000390955.2
ENTPD1	ENST00000371207.8	c.52+65T>C		intron_variant	Intron 1 of 9	2		ENSP00000360250.3
ENTPD1	ENST00000543964.6	c.-181+65T>C		intron_variant	Intron 1 of 8	2		ENSP00000442968.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5136 AN: 151876 Hom.: 119 Cov.: 31

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0429 AC: 58335 AN: 1359282 Hom.: 1421 Cov.: 25 AF XY: 0.0424 AC XY: 28508 AN XY: 672240

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0578

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.0138

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0480

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0338 AC: 5131 AN: 151994 Hom.: 119 Cov.: 31 AF XY: 0.0332 AC XY: 2470 AN XY: 74288

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00996

Gnomad4 FIN AF: 0.0380

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0448 Hom.: 167

Bravo AF: 0.0318

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3176892; hg19: chr10-97515588;