22-17085042-T-C

Variant summary

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

The NM_014339.7(IL17RA):c.-50T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,296,336 control chromosomes in the GnomAD database, including 424,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53564 hom., cov: 34)
  • Exomes 𝑓: 0.80 (370753 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

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=-0.88).
• BP6: Variant 22-17085042-T-C is Benign according to our data. Variant chr22-17085042-T-C is described in ClinVar as [Benign]. Clinvar id is 340557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RA	NM_014339.7	c.-50T>C		5_prime_UTR_variant	1/13	ENST00000319363.11
IL17RA	NM_001289905.2	c.-50T>C		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11	c.-50T>C		5_prime_UTR_variant	1/13	1	NM_014339.7	P2

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126593 AN: 152048 Hom.: 53512 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.818

GnomAD3 exomes AF: 0.803 AC: 878 AN: 1094 Hom.: 354 AF XY: 0.814 AC XY: 477 AN XY: 586

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 0.763

Gnomad ASJ exome AF: 0.833

Gnomad EAS exome AF: 0.662

Gnomad SAS exome AF: 0.738

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.804 AC: 919517 AN: 1144172 Hom.: 370753 Cov.: 32 AF XY: 0.804 AC XY: 440659 AN XY: 548260

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.817

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.791

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.806

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.833 AC: 126695 AN: 152164 Hom.: 53564 Cov.: 34 AF XY: 0.829 AC XY: 61700 AN XY: 74398

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.817

Alfa AF: 0.802 Hom.: 18441

Bravo AF: 0.821

Asia WGS AF: 0.680 AC: 2365 AN: 3478

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 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. 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	-0.88
Cadd	Benign	6.4
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs917864; hg19: chr22-17565932;