rs1653624

Variant names:

• chr12-121184717-T-A
• rs1653624
• NM_002562.6:c.1703T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-121184717-T-A
• chr12-121184717-T-C
• chr12-121184717-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_002562.6(P2RX7):​c.1703T>A​(p.Ile568Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,562,934 control chromosomes in the GnomAD database, including 424 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 0.015 (24 hom., cov: 33)
  • Exomes 𝑓: 0.022 (400 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 86 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11476803).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.015 (2289/152316) while in subpopulation NFE AF = 0.0245 (1667/68016). AF 95% confidence interval is 0.0235. There are 24 homozygotes in GnomAd4. There are 1070 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

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.1703T>A	p.Ile568Asn	missense	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.2021T>A		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1937T>A		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.1703T>A	p.Ile568Asn	missense	Exon 13 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*1156T>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1458T>A		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2289 AN: 152198 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.0220 AC: 31022 AN: 1410618 Hom.: 400 Cov.: 37 AF XY: 0.0212 AC XY: 14797 AN XY: 697236

African (AFR) AF: 0.00260 AC: 83 AN: 31968

American (AMR) AF: 0.00496 AC: 184 AN: 37122

Ashkenazi Jewish (ASJ) AF: 0.00457 AC: 116 AN: 25392

East Asian (EAS) AF: 0.0000548 AC: 2 AN: 36482

South Asian (SAS) AF: 0.00329 AC: 266 AN: 80738

European-Finnish (FIN) AF: 0.0291 AC: 1438 AN: 49482

Middle Eastern (MID) AF: 0.000876 AC: 5 AN: 5708

European-Non Finnish (NFE) AF: 0.0258 AC: 27995 AN: 1085258

Other (OTH) AF: 0.0160 AC: 933 AN: 58468

GnomAD4 genome AF: 0.0150 AC: 2289 AN: 152316 Hom.: 24 Cov.: 33 AF XY: 0.0144 AC XY: 1070 AN XY: 74490

African (AFR) AF: 0.00385 AC: 160 AN: 41584

American (AMR) AF: 0.00798 AC: 122 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1667 AN: 68016

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.0183 Hom.: 8

Bravo AF: 0.0130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DEOGEN2	Uncertain	0.48	T
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.11	T
PhyloP100		3.0
Sift4G	Pathogenic	0.0010	D
Vest4		0.72
gMVP		0.70

Splicing

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

Other links and lift over

dbSNP: rs1653624; hg19: chr12-121622520;