rs3949478

Variant names:

• chr10-95713457-A-G
• rs3949478
• ENST00000453258.6:c.37+1464A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-95713457-A-G
• chr10-95713457-A-T

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+1464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,132 control chromosomes in the GnomAD database, including 41,168 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 0.73 (41168 hom., cov: 33)
• Consequence: ENTPD1 NM_001098175.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 6 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: Baylor College of Medicine Research Center, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• 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=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 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+1464A>G		intron	N/A	NP_001091645.1	P49961-2
	ENTPD1	NM_001440933.1		c.37+1464A>G		intron	N/A	NP_001427862.1
	ENTPD1	NM_001440934.1		c.37+1464A>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+1464A>G		intron	N/A	ENSP00000390955.2	P49961-2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110994 AN: 152014 Hom.: 41163 Cov.: 33

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.730 AC: 111042 AN: 152132 Hom.: 41168 Cov.: 33 AF XY: 0.727 AC XY: 54051 AN XY: 74378

African (AFR) AF: 0.595 AC: 24657 AN: 41462

American (AMR) AF: 0.757 AC: 11582 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2872 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4043 AN: 5182

South Asian (SAS) AF: 0.656 AC: 3165 AN: 4828

European-Finnish (FIN) AF: 0.754 AC: 7969 AN: 10574

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54231 AN: 68004

Other (OTH) AF: 0.744 AC: 1572 AN: 2112

Alfa AF: 0.783 Hom.: 71332

Bravo AF: 0.729

Asia WGS AF: 0.693 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3949478;

hg19: chr10-97473214;