rs1933166

Variant names:

• chr10-95727605-A-G
• rs1933166
• ENST00000453258.6:c.37+15612A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098175.2(ENTPD1):​c.37+15612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,118 control chromosomes in the GnomAD database, including 2,494 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 0.16 (2494 hom., cov: 32)
• Consequence: ENTPD1 NM_001098175.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 64

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, Baylor College of Medicine Research Center, Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098175.2. 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
	ENTPD1	NM_001098175.2		c.37+15612A>G		intron	N/A	NP_001091645.1	P49961-2
	ENTPD1	NM_001440933.1		c.37+15612A>G		intron	N/A	NP_001427862.1
	ENTPD1	NM_001440934.1		c.37+15612A>G		intron	N/A	NP_001427863.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	ENST00000453258.6	TSL:1	c.37+15612A>G		intron	N/A	ENSP00000390955.2	P49961-2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24174 AN: 152000 Hom.: 2486 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24233 AN: 152118 Hom.: 2494 Cov.: 32 AF XY: 0.163 AC XY: 12108 AN XY: 74374

African (AFR) AF: 0.281 AC: 11649 AN: 41462

American (AMR) AF: 0.150 AC: 2299 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.173 AC: 893 AN: 5172

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4826

European-Finnish (FIN) AF: 0.135 AC: 1426 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0892 AC: 6066 AN: 68000

Other (OTH) AF: 0.154 AC: 324 AN: 2110

Alfa AF: 0.114 Hom.: 1978

Bravo AF: 0.163

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1933166; hg19: chr10-97487362;