dbSNP rs1351337413: IL17RA:p.Arg5Ser (chr22-17085104-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014339.7(IL17RA):c.13C>A(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL17RA
NM_014339.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.87

Publications

1 publications found

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]

IL17RA Gene-Disease associations (from GenCC):

immunodeficiency 51
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
chronic mucocutaneous candidiasis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IL17RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08428225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 12		NP_001276834.1	Q96F46-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

18690

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1209620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

586964

African (AFR)

AF:

0.00

AC:

AN:

24382

American (AMR)

AF:

0.00

AC:

AN:

12514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17178

East Asian (EAS)

AF:

0.00

AC:

AN:

27480

South Asian (SAS)

AF:

0.00

AC:

AN:

53980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

990396

Other (OTH)

AF:

0.00

AC:

AN:

49544

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.22

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.099

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L

PhyloP100

-2.9

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.015

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.31

T;T

Polyphen

0.011

B;.

Vest4

0.077

MutPred

0.17

Gain of glycosylation at R5 (P = 0.0038);Gain of glycosylation at R5 (P = 0.0038);

MVP

0.067

MPC

0.21

ClinPred

0.099

GERP RS

-0.32

PromoterAI

0.015

Neutral

(source)

Varity_R

0.13

gMVP

0.62

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over