10-95869237-A-C

Variant names:

• chr10-95869237-A-C
• rs2226163
• NM_001776.6:c.*2854A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001776.6(ENTPD1):​c.*2854A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 130,584 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000077 (0 hom., cov: 21)
• Consequence: ENTPD1 NM_001776.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 9 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]

ENSG00000270099 (HGNC:):

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD1	NM_001776.6	c.*2854A>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000371205.5	NP_001767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD1	ENST00000371205.5	c.*2854A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_001776.6	ENSP00000360248.4
ENSG00000270099	ENST00000491114.1	n.171+4376A>C		intron_variant	Intron 2 of 6	5		ENSP00000473305.1

Frequencies

GnomAD3 genomes AF: 0.00000766 AC: 1 AN: 130584 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 8

GnomAD4 genome AF: 0.00000766 AC: 1 AN: 130584 Hom.: 0 Cov.: 21 AF XY: 0.0000161 AC XY: 1 AN XY: 61982

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33894

American (AMR) AF: 0.0000798 AC: 1 AN: 12538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3280

East Asian (EAS) AF: 0.00 AC: 0 AN: 4434

South Asian (SAS) AF: 0.00 AC: 0 AN: 4162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63338

Other (OTH) AF: 0.00 AC: 0 AN: 1800

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.42
PhyloP100		-0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2226163; hg19: chr10-97628994;