rs879575

Variant names:

• chr22-17108677-C-T
• rs879575
• NM_014339.7:c.1458C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):​c.1458C>T​(p.Ile486Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,607,998 control chromosomes in the GnomAD database, including 41,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3323 hom., cov: 34)
  • Exomes 𝑓: 0.22 (38182 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: 1.98
• Publications: 24 publications found

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 22-17108677-C-T is Benign according to our data. Variant chr22-17108677-C-T is described in ClinVar as Benign. ClinVar VariationId is 340598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1458C>T	p.Ile486Ile	synonymous_variant	Exon 13 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.1356C>T	p.Ile452Ile	synonymous_variant	Exon 12 of 12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1458C>T	p.Ile486Ile	synonymous_variant	Exon 13 of 13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.1356C>T	p.Ile452Ile	synonymous_variant	Exon 12 of 12	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31020 AN: 152148 Hom.: 3324 Cov.: 34

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.193 AC: 47167 AN: 244674 AF XY: 0.197

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0510

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.224 AC: 326044 AN: 1455732 Hom.: 38182 Cov.: 62 AF XY: 0.223 AC XY: 161699 AN XY: 724526

African (AFR) AF: 0.167 AC: 5592 AN: 33466

American (AMR) AF: 0.115 AC: 5159 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6351 AN: 26120

East Asian (EAS) AF: 0.0508 AC: 2018 AN: 39690

South Asian (SAS) AF: 0.171 AC: 14789 AN: 86248

European-Finnish (FIN) AF: 0.217 AC: 10356 AN: 47748

Middle Eastern (MID) AF: 0.221 AC: 1272 AN: 5768

European-Non Finnish (NFE) AF: 0.241 AC: 267483 AN: 1111680

Other (OTH) AF: 0.216 AC: 13024 AN: 60306

GnomAD4 genome AF: 0.204 AC: 31028 AN: 152266 Hom.: 3323 Cov.: 34 AF XY: 0.201 AC XY: 14966 AN XY: 74450

African (AFR) AF: 0.169 AC: 7031 AN: 41550

American (AMR) AF: 0.158 AC: 2423 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.0576 AC: 298 AN: 5178

South Asian (SAS) AF: 0.172 AC: 833 AN: 4834

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10614

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16547 AN: 67992

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.225 Hom.: 9292

Bravo AF: 0.195

Asia WGS AF: 0.134 AC: 467 AN: 3478

EpiCase AF: 0.242

EpiControl AF: 0.244

ClinVar

Significance: Benign

Submissions summary: Benign:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

not provided Benign:1 Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial Candidiasis, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 51 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs879575; hg19: chr22-17589567; COSMIC: COSV60051845;