rs879575

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014339.7(IL17RA):c.1458C>T(p.Ile486=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.98

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 340598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17108677-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
IL17RA	NM_014339.7 linkuse as main transcript	c.1458C>T	p.Ile486=	synonymous_variant	13/13	ENST00000319363.11
IL17RA	NM_001289905.2 linkuse as main transcript	c.1356C>T	p.Ile452=	synonymous_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11 linkuse as main transcript	c.1458C>T	p.Ile486=	synonymous_variant	13/13	1	NM_014339.7	P2	Q96F46-1
IL17RA	ENST00000612619.2 linkuse as main transcript	c.1356C>T	p.Ile452=	synonymous_variant	12/12	5		A2	Q96F46-2

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31020

AN:

152148

Hom.:

3324

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.193

AC:

47167

AN:

244674

Hom.:

5055

AF XY:

0.197

AC XY:

26216

AN XY:

133032

show subpopulations

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 SAS exome

AF:

0.174

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.:

AF XY:

0.223

AC XY:

161699

AN XY:

724526

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.0508

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.204

AC:

31028

AN:

152266

Hom.:

3323

Cov.:

AF XY:

0.201

AC XY:

14966

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.0576

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.233

Hom.:

5755

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:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

Familial Candidiasis, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Immunodeficiency 51

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

Cadd

Benign

9.1

Dann

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over