rs3751144

Variant names:

• chr12-121184436-C-T
• rs3751144
• NM_002562.6:c.1422C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002562.6(P2RX7):​c.1422C>T​(p.Pro474Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,982 control chromosomes in the GnomAD database, including 10,364 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 0.12 (1436 hom., cov: 32)
  • Exomes 𝑓: 0.094 (8928 hom.)
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.23
• Publications: 19 publications found

Genes affected

P2RX7 (HGNC:8537): (purinergic receptor P2X 7) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

ENSG00000286248 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-6.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. 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
	P2RX7	NM_002562.6	MANE Select	c.1422C>T	p.Pro474Pro	synonymous	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1740C>T		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1656C>T		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1422C>T	p.Pro474Pro	synonymous	Exon 13 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*875C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1177C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18565 AN: 152040 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.141 AC: 35400 AN: 251364 AF XY: 0.131

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.173

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0751

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0942 AC: 137726 AN: 1461824 Hom.: 8928 Cov.: 37 AF XY: 0.0939 AC XY: 68274 AN XY: 727222

African (AFR) AF: 0.153 AC: 5116 AN: 33480

American (AMR) AF: 0.338 AC: 15132 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0601 AC: 1571 AN: 26136

East Asian (EAS) AF: 0.156 AC: 6182 AN: 39700

South Asian (SAS) AF: 0.150 AC: 12936 AN: 86256

European-Finnish (FIN) AF: 0.127 AC: 6768 AN: 53400

Middle Eastern (MID) AF: 0.0638 AC: 368 AN: 5768

European-Non Finnish (NFE) AF: 0.0752 AC: 83607 AN: 1111978

Other (OTH) AF: 0.100 AC: 6046 AN: 60396

GnomAD4 genome AF: 0.122 AC: 18609 AN: 152158 Hom.: 1436 Cov.: 32 AF XY: 0.126 AC XY: 9374 AN XY: 74372

African (AFR) AF: 0.157 AC: 6508 AN: 41518

American (AMR) AF: 0.221 AC: 3369 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3468

East Asian (EAS) AF: 0.163 AC: 841 AN: 5160

South Asian (SAS) AF: 0.162 AC: 782 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0777 AC: 5284 AN: 68012

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0937 Hom.: 3434

Bravo AF: 0.131

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.0671

EpiControl AF: 0.0708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.058
DANN	Benign	0.84
PhyloP100		-6.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3751144; hg19: chr12-121622239; COSMIC: COSV55853264;