Genetic Variant ENSG00000291240:n.1732+1143A>G (chr22-21028193-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000706202.1(ENSG00000291240):n.1732+1143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,214 control chromosomes in the GnomAD database, including 3,880 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 0.19 ( 3879 hom., cov: 33)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

ENSG00000291240
ENST00000706202.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.948

Publications

10 publications found

Variant links:

Genes affected

ENSG00000291240 (HGNC:):

ENSG00000291240 links:

P2RX6 (HGNC:8538): (purinergic receptor P2X 6) The protein encoded by this gene belongs to the family of P2X receptors, which are ATP-gated ion channels and mediate rapid and selective permeability to cations. This gene is predominantly expressed in skeletal muscle, and regulated by p53. The encoded protein is associated with VE-cadherin at the adherens junctions of human umbilical vein endothelial cells. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 22, has been identified. [provided by RefSeq, Apr 2009]

P2RX6 Gene-Disease associations (from GenCC):

myopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

P2RX6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706202.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
P2RX6	NM_005446.5	MANE Select	c.*1576T>C	downstream_gene	N/A	NP_005437.2
P2RX6	NM_001394691.1		c.*1467T>C	downstream_gene	N/A	NP_001381620.1
P2RX6	NM_001394692.1		c.*1576T>C	downstream_gene	N/A	NP_001381621.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENSG00000291240	ENST00000706202.1		n.1732+1143A>G	intron	N/A	ENSP00000516280.1
P2RX6	ENST00000413302.7	TSL:1 MANE Select	c.*1576T>C	downstream_gene	N/A	ENSP00000416193.2
P2RX6	ENST00000422210.5	TSL:1	n.*1883T>C	downstream_gene	N/A	ENSP00000407920.1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29253

AN:

151982

Hom.:

3872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.0926

Gnomad OTH

AF:

0.199

GnomAD4 exome

AF:

0.132

AC:

AN:

114

Hom.:

Cov.:

AF XY:

0.118

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.193

AC:

29292

AN:

152100

Hom.:

3879

Cov.:

AF XY:

0.201

AC XY:

14957

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.296

AC:

12279

AN:

41456

American (AMR)

AF:

0.250

AC:

3827

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

495

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2881

AN:

5160

South Asian (SAS)

AF:

0.324

AC:

1567

AN:

4832

European-Finnish (FIN)

AF:

0.135

AC:

1428

AN:

10614

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0926

AC:

6293

AN:

67970

Other (OTH)

AF:

0.207

AC:

437

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1097

2194

3291

4388

5485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

3057

Bravo

AF:

0.203

Asia WGS

AF:

0.434

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.26

(source)

DANN

Benign

0.77

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over