rs146292661

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014339.7(IL17RA):c.1689C>T(p.Gly563Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,611,472 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0021 ( 3 hom. )

Consequence

IL17RA
NM_014339.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.47

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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 22-17108908-C-T is Benign according to our data. Variant chr22-17108908-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 340603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00177 (269/152334) while in subpopulation NFE AF = 0.00251 (171/68022). AF 95% confidence interval is 0.00221. There are 0 homozygotes in GnomAd4. There are 129 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.1689C>T	p.Gly563Gly	synonymous_variant	Exon 13 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.1587C>T	p.Gly529Gly	synonymous_variant	Exon 12 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.1689C>T	p.Gly563Gly	synonymous_variant	Exon 13 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1
IL17RA	ENST00000612619.2 link	c.1587C>T	p.Gly529Gly	synonymous_variant	Exon 12 of 12	5		ENSP00000479970.1		Q96F46-2

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00163

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00206

AC:

494

AN:

240352

AF XY:

0.00187

show subpopulations

Gnomad AFR exome

AF:

0.000268

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00308

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00305

GnomAD4 exome

AF:

0.00211

AC:

3073

AN:

1459138

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1509

AN XY:

725876

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33456

American (AMR)

AF:

0.00220

AC:

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.000477

AC:

AN:

86034

European-Finnish (FIN)

AF:

0.00320

AC:

167

AN:

52124

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00228

AC:

2534

AN:

1111314

Other (OTH)

AF:

0.00237

AC:

143

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152334

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41586

American (AMR)

AF:

0.00163

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00251

AC:

171

AN:

68022

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL17RA: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Immunodeficiency 51

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.82

(source)

DANN

Benign

0.57

PhyloP100

-1.5

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

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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