rs41396346

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014339.7(IL17RA):​c.1407C>G​(p.Cys469Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C469C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

IL17RA
NM_014339.7 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.133
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21899658).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL17RANM_014339.7 linkc.1407C>G p.Cys469Trp missense_variant Exon 13 of 13 ENST00000319363.11 NP_055154.3 Q96F46-1
IL17RANM_001289905.2 linkc.1305C>G p.Cys435Trp missense_variant Exon 12 of 12 NP_001276834.1 Q96F46-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL17RAENST00000319363.11 linkc.1407C>G p.Cys469Trp missense_variant Exon 13 of 13 1 NM_014339.7 ENSP00000320936.6 Q96F46-1
IL17RAENST00000612619.2 linkc.1305C>G p.Cys435Trp missense_variant Exon 12 of 12 5 ENSP00000479970.1 Q96F46-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452690
Hom.:
0
Cov.:
61
AF XY:
0.00000138
AC XY:
1
AN XY:
723138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
17
DANN
Benign
0.93
DEOGEN2
Uncertain
0.59
D;.
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.78
T;T
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-3.6
D;.
REVEL
Benign
0.17
Sift
Benign
0.033
D;.
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;.
Vest4
0.34
MutPred
0.53
Gain of MoRF binding (P = 0.0168);.;
MVP
0.20
MPC
0.88
ClinPred
0.73
D
GERP RS
-3.4
Varity_R
0.43
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-17589516; API