rs503720

Positions:

• chr12-121167271-G-A
• chr12-121167271-G-C

Variant summary

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

The NM_002562.6(P2RX7):​c.745-217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,764 control chromosomes in the GnomAD database, including 8,245 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 0.32 (8245 hom., cov: 30)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.745-217G>A		intron_variant		ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+36227C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.745-217G>A		intron_variant		1	NM_002562.6	ENSP00000330696	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48712 AN: 151646 Hom.: 8229 Cov.: 30

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48769 AN: 151764 Hom.: 8245 Cov.: 30 AF XY: 0.319 AC XY: 23668 AN XY: 74164

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.309

Alfa AF: 0.297 Hom.: 9265

Bravo AF: 0.309

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.079
DANN	Benign	0.70

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: rs503720; hg19: chr12-121605074;