rs143008696

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014339.7(IL17RA):c.152C>T(p.Thr51Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,613,292 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T51T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 10 hom. )

Consequence

IL17RA
NM_014339.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -1.25

Publications

15 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011457801).

BP6

Variant 22-17097075-C-T is Benign according to our data. Variant chr22-17097075-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 340565.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00225 (343/152226) while in subpopulation NFE AF = 0.00413 (281/68022). AF 95% confidence interval is 0.00373. There are 1 homozygotes in GnomAd4. There are 161 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.152C>T	p.Thr51Met	missense_variant	Exon 2 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.152C>T	p.Thr51Met	missense_variant	Exon 2 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.152C>T	p.Thr51Met	missense_variant	Exon 2 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00178

AC:

447

AN:

251486

AF XY:

0.00161

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00382

AC:

5580

AN:

1461066

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2678

AN XY:

726894

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33472

American (AMR)

AF:

0.00143

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.000468

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00462

AC:

5134

AN:

1111294

Other (OTH)

AF:

0.00534

AC:

322

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

249

497

746

994

1243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152226

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41528

American (AMR)

AF:

0.00163

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00413

AC:

281

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00324

Hom.:

Bravo

AF:

0.00242

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.00174

AC:

211

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00425

EpiControl

AF:

0.00296

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Immunodeficiency 51

Uncertain:1Benign:2

Mar 30, 2021

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL17RA NM_014339.6 exon 2 p.Thr51Met (c.152C>T):This variant has not been reported in the literature but is present in 0.3% (409/129168) of European alleles including 1 homozygote, in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/22-17577965-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:340565). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

IL17RA-related disorder

Uncertain:1

Jun 28, 2024

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The IL17RA c.152C>T variant is predicted to result in the amino acid substitution p.Thr51Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.32% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including one homozygous individual. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

-1.3

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.099

Sift

Benign

0.10

T;.

Sift4G

Benign

0.18

T;T

Polyphen

1.0

D;.

Vest4

0.40

MVP

0.040

MPC

0.21

ClinPred

0.018

GERP RS

-6.8

Varity_R

0.053

gMVP

0.55

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs143008696

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over