dbSNP rs41529049: IL17RA:p.Thr498Asn (chr22-17108712-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014339.7(IL17RA):c.1493C>A(p.Thr498Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T498I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL17RA
NM_014339.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3951962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.1493C>A	p.Thr498Asn	missense_variant	Exon 13 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2 link	c.1391C>A	p.Thr464Asn	missense_variant	Exon 12 of 12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.1493C>A	p.Thr498Asn	missense_variant	Exon 13 of 13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2 link	c.1391C>A	p.Thr464Asn	missense_variant	Exon 12 of 12	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458378

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111836

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PhyloP100

2.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.098

Sift

Benign

0.14

T;.

Sift4G

Benign

0.10

T;T

Polyphen

0.84

P;.

Vest4

0.34

MutPred

0.42

Loss of phosphorylation at T498 (P = 0.0853);.;

MVP

0.26

MPC

0.72

ClinPred

0.70

GERP RS

-0.86

Varity_R

0.13

gMVP

0.55

Mutation Taster

=91/9

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

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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