rs1621388

Variant names:

• chr12-121184760-G-A
• rs1621388
• NM_002562.6:c.1746G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-121184760-G-A
• chr12-121184760-G-C
• chr12-121184760-G-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.1746G>A​(p.Pro582Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,552,404 control chromosomes in the GnomAD database, including 118,313 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 0.39 (11789 hom., cov: 32)
  • Exomes 𝑓: 0.39 (106524 hom.)
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 23 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=-0.59).
• BP7: Synonymous conserved (PhyloP=0.265 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 13 of 13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1746G>A	p.Pro582Pro	synonymous_variant	Exon 13 of 13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58657 AN: 151942 Hom.: 11767 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.362

GnomAD2 exomes AF: 0.344 AC: 54214 AN: 157728 AF XY: 0.351

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.386 AC: 540202 AN: 1400344 Hom.: 106524 Cov.: 41 AF XY: 0.386 AC XY: 266419 AN XY: 690920

African (AFR) AF: 0.463 AC: 14670 AN: 31664

American (AMR) AF: 0.186 AC: 6670 AN: 35912

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 8962 AN: 25296

East Asian (EAS) AF: 0.143 AC: 5113 AN: 35854

South Asian (SAS) AF: 0.385 AC: 30638 AN: 79512

European-Finnish (FIN) AF: 0.446 AC: 21745 AN: 48770

Middle Eastern (MID) AF: 0.360 AC: 2043 AN: 5670

European-Non Finnish (NFE) AF: 0.397 AC: 428719 AN: 1079590

Other (OTH) AF: 0.373 AC: 21642 AN: 58076

GnomAD4 genome AF: 0.386 AC: 58725 AN: 152060 Hom.: 11789 Cov.: 32 AF XY: 0.381 AC XY: 28305 AN XY: 74334

African (AFR) AF: 0.443 AC: 18359 AN: 41452

American (AMR) AF: 0.242 AC: 3698 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4824

European-Finnish (FIN) AF: 0.449 AC: 4748 AN: 10578

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27149 AN: 67984

Other (OTH) AF: 0.357 AC: 752 AN: 2106

Alfa AF: 0.374 Hom.: 8253

Bravo AF: 0.369

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.27
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: rs1621388; hg19: chr12-121622563; COSMIC: COSV108031464; COSMIC: COSV108031464;