rs1653583

Variant names:

• chr12-121160849-G-A
• rs1653583
• NM_002562.6:c.364-53G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-121160849-G-A
• chr12-121160849-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.364-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,325,298 control chromosomes in the GnomAD database, including 5,203 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 0.10 (965 hom., cov: 32)
  • Exomes 𝑓: 0.080 (4238 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

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]

LOC105370032 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.364-53G>A		intron_variant	Intron 3 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.364-53G>A		intron_variant	Intron 3 of 12	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15509 AN: 152048 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0927

GnomAD4 exome AF: 0.0799 AC: 93709 AN: 1173132 Hom.: 4238 AF XY: 0.0807 AC XY: 48277 AN XY: 597970

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0378

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.0624

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0694

Gnomad4 NFE exome AF: 0.0779

Gnomad4 OTH exome AF: 0.0824

GnomAD4 genome AF: 0.102 AC: 15523 AN: 152166 Hom.: 965 Cov.: 32 AF XY: 0.0992 AC XY: 7380 AN XY: 74412

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0740 Hom.: 254

Bravo AF: 0.103

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs1653583; hg19: chr12-121598652; COSMIC: COSV55855264;