rs1057518747
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014339.7(IL17RA):c.769_773delCCAGA(p.Pro257ArgfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
IL17RA
NM_014339.7 frameshift
NM_014339.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.378
Publications
2 publications found
Genes affected
IL17RA (HGNC:5985): (interleukin 17 receptor A) Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]
IL17RA Gene-Disease associations (from GenCC):
- immunodeficiency 51Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- chronic mucocutaneous candidiasisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-17103494-CCCAGA-C is Pathogenic according to our data. Variant chr22-17103494-CCCAGA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 372208.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IL17RA | NM_014339.7 | c.769_773delCCAGA | p.Pro257ArgfsTer16 | frameshift_variant | Exon 8 of 13 | ENST00000319363.11 | NP_055154.3 | |
| IL17RA | NM_001289905.2 | c.769_773delCCAGA | p.Pro257ArgfsTer16 | frameshift_variant | Exon 8 of 12 | NP_001276834.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461126Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726858 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1461126
Hom.:
AF XY:
AC XY:
1
AN XY:
726858
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33404
American (AMR)
AF:
AC:
0
AN:
44692
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
0
AN:
86116
European-Finnish (FIN)
AF:
AC:
0
AN:
53362
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111626
Other (OTH)
AF:
AC:
0
AN:
60362
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0186682), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.358
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 51 Pathogenic:1
Dec 19, 2016
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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