17-3682483-C-G

Variant names:

• chr17-3682483-C-G
• rs222775
• NM_002561.4:c.982-505G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002561.4(P2RX5):​c.982-505G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 203,722 control chromosomes in the GnomAD database, including 22,315 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 (16050 hom., cov: 33)
  • Exomes 𝑓: 0.49 (6265 hom.)
• Consequence: P2RX5 NM_002561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 1 publications found

Genes affected

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002561.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX5	NM_002561.4	MANE Select	c.982-505G>C		intron	N/A	NP_002552.2
	P2RX5	NM_001204519.2		c.979-505G>C		intron	N/A	NP_001191448.1	Q93086-1
	P2RX5	NM_001204520.2		c.910-505G>C		intron	N/A	NP_001191449.1	Q93086-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX5	ENST00000225328.10	TSL:1 MANE Select	c.982-505G>C		intron	N/A	ENSP00000225328.5	Q93086-3
	P2RX5	ENST00000697413.1		c.1048-505G>C		intron	N/A	ENSP00000513301.1	Q93086-6
	P2RX5	ENST00000547178.5	TSL:1	c.979-505G>C		intron	N/A	ENSP00000448355.1	Q93086-1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67135 AN: 152022 Hom.: 16052 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.487 AC: 25096 AN: 51582 Hom.: 6265 Cov.: 0 AF XY: 0.488 AC XY: 13432 AN XY: 27528

African (AFR) AF: 0.217 AC: 405 AN: 1870

American (AMR) AF: 0.474 AC: 1725 AN: 3638

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 517 AN: 1052

East Asian (EAS) AF: 0.459 AC: 1431 AN: 3120

South Asian (SAS) AF: 0.516 AC: 4089 AN: 7922

European-Finnish (FIN) AF: 0.493 AC: 816 AN: 1654

Middle Eastern (MID) AF: 0.500 AC: 85 AN: 170

European-Non Finnish (NFE) AF: 0.501 AC: 14834 AN: 29586

Other (OTH) AF: 0.465 AC: 1194 AN: 2570

GnomAD4 genome AF: 0.441 AC: 67163 AN: 152140 Hom.: 16050 Cov.: 33 AF XY: 0.444 AC XY: 33021 AN XY: 74378

African (AFR) AF: 0.240 AC: 9974 AN: 41516

American (AMR) AF: 0.490 AC: 7487 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1800 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2383 AN: 5172

South Asian (SAS) AF: 0.541 AC: 2607 AN: 4818

European-Finnish (FIN) AF: 0.527 AC: 5577 AN: 10582

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35531 AN: 67986

Other (OTH) AF: 0.468 AC: 988 AN: 2112

Alfa AF: 0.468 Hom.: 2166

Bravo AF: 0.429

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs222775; hg19: chr17-3585777; COSMIC: COSV56593653; COSMIC: COSV56593653;