rs10160951

Positions:

• chr12-121180454-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.1289C>G​(p.Pro430Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,517,598 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.042 (408 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (404 hom.)
• Consequence: P2RX7 NM_002562.6 missense, splice_region
• Scores: Splicing: ADA: 0.05033
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018902719).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1289C>G	p.Pro430Arg	missense_variant, splice_region_variant	Exon 12 of 13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1289C>G	p.Pro430Arg	missense_variant, splice_region_variant	Exon 12 of 13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6380 AN: 151036 Hom.: 409 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0352

GnomAD3 exomes AF: 0.0136 AC: 2930 AN: 215124 Hom.: 165 AF XY: 0.0103 AC XY: 1205 AN XY: 117246

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00275

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00240

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.00568 AC: 7755 AN: 1366464 Hom.: 404 Cov.: 22 AF XY: 0.00516 AC XY: 3524 AN XY: 683250

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00274

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000924

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00157

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0423 AC: 6387 AN: 151134 Hom.: 408 Cov.: 31 AF XY: 0.0399 AC XY: 2943 AN XY: 73766

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.0348

Alfa AF: 0.00833 Hom.: 57

Bravo AF: 0.0483

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.138 AC: 607

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.0145 AC: 1765

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.078
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.31	T
REVEL	Benign	0.12
Sift4G	Benign	0.26	T
Polyphen		0.26	B
Vest4		0.081
ClinPred		0.013	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.050
dbscSNV1_RF	Benign	0.37
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: rs10160951; hg19: chr12-121618257;