22-17084998-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000694948.1(IL17RA):n.5C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,243,000 control chromosomes in the GnomAD database, including 154,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13852 hom., cov: 32)
  • Exomes 𝑓: 0.50 (141070 hom.)
• Consequence: IL17RA ENST00000694948.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 22-17084998-C-A is Benign according to our data. Variant chr22-17084998-C-A is described in ClinVar as [Benign]. Clinvar id is 340556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RA	NM_014339.7			upstream_gene_variant		ENST00000319363.11
IL17RA	NM_001289905.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11			upstream_gene_variant		1	NM_014339.7	P2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59026 AN: 151860 Hom.: 13856 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.503 AC: 549019 AN: 1091024 Hom.: 141070 Cov.: 19 AF XY: 0.504 AC XY: 262939 AN XY: 521304

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.388 AC: 59013 AN: 151976 Hom.: 13852 Cov.: 32 AF XY: 0.388 AC XY: 28809 AN XY: 74294

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.431

Alfa AF: 0.387 Hom.: 2560

Bravo AF: 0.367

Asia WGS AF: 0.319 AC: 1107 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -

Familial Candidiasis, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.16
Dann	Benign	0.45

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: rs13053694; hg19: chr22-17565888;