rs2229151

chr22-17108407-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):c.1188G>A(p.Leu396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,614,048 control chromosomes in the GnomAD database, including 4,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (405 hom., cov: 34)
  • Exomes 𝑓: 0.028 (3902 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.36

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-17108407-G-A is Benign according to our data. Variant chr22-17108407-G-A is described in ClinVar as [Benign]. Clinvar id is 340594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RA	NM_014339.7	c.1188G>A	p.Leu396=	synonymous_variant	13/13	ENST00000319363.11
IL17RA	NM_001289905.2	c.1086G>A	p.Leu362=	synonymous_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11	c.1188G>A	p.Leu396=	synonymous_variant	13/13	1	NM_014339.7	P2
IL17RA	ENST00000612619.2	c.1086G>A	p.Leu362=	synonymous_variant	12/12	5		A2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4492 AN: 152196 Hom.: 406 Cov.: 34

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00454

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0757 AC: 19011 AN: 251140 Hom.: 2086 AF XY: 0.0722 AC XY: 9800 AN XY: 135792

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.313

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.0396

Gnomad NFE exome AF: 0.00549

Gnomad OTH exome AF: 0.0545

GnomAD4 exome AF: 0.0279 AC: 40839 AN: 1461734 Hom.: 3902 Cov.: 62 AF XY: 0.0304 AC XY: 22117 AN XY: 727172

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0412

Gnomad4 NFE exome AF: 0.00354

Gnomad4 OTH exome AF: 0.0404

GnomAD4 genome AF: 0.0296 AC: 4501 AN: 152314 Hom.: 405 Cov.: 34 AF XY: 0.0350 AC XY: 2604 AN XY: 74472

Gnomad4 AFR AF: 0.00447

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.00454

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0221 Hom.: 165

Bravo AF: 0.0342

Asia WGS AF: 0.209 AC: 727 AN: 3478

EpiCase AF: 0.00333

EpiControl AF: 0.00350

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.27
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs2229151; hg19: chr22-17589297; COSMIC: COSV60053540;