rs1653625

chr12-121185082-C-Achr12-121185082-C-G

Variant summary

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

The NM_002562.6(P2RX7):c.*280C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 195,154 control chromosomes in the GnomAD database, including 12,502 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 0.44 (12092 hom., cov: 26)
  • Exomes 𝑓: 0.22 (410 hom.)
• Consequence: P2RX7 NM_002562.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.*280C>A		3_prime_UTR_variant	13/13	ENST00000328963.10
LOC105370032	XR_001749352.3	n.327+18416G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.*280C>A		3_prime_UTR_variant	13/13	1	NM_002562.6	P1
P2RX7	ENST00000261826.10	c.*1521C>A		3_prime_UTR_variant, NMD_transcript_variant	12/12	1
	ENST00000652651.1	n.3548+1119G>T		intron_variant, non_coding_transcript_variant
P2RX7	ENST00000537312.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 57649 AN: 132502 Hom.: 12068 Cov.: 26

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.219 AC: 13687 AN: 62560 Hom.: 410 Cov.: 0 AF XY: 0.219 AC XY: 6978 AN XY: 31822

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.435 AC: 57727 AN: 132594 Hom.: 12092 Cov.: 26 AF XY: 0.434 AC XY: 27946 AN XY: 64324

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.74
Dann	Benign	0.33

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: rs1653625; hg19: chr12-121622885;