rs917865

Positions:

• chr22-17085084-G-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.-8G>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 1,315,154 control chromosomes in the GnomAD database, including 430,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53550 hom., cov: 34)
  • Exomes 𝑓: 0.80 (377345 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.04

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-17085084-G-C is Benign according to our data. Variant chr22-17085084-G-C is described in ClinVar as [Benign]. Clinvar id is 340561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17085084-G-C is described in Lovd as [Benign].
• 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	Protein	UniProt
IL17RA	NM_014339.7	c.-8G>C		5_prime_UTR_variant	1/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-8G>C		5_prime_UTR_variant	1/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363	c.-8G>C		5_prime_UTR_variant	1/13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126564 AN: 152026 Hom.: 53500 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.818

GnomAD3 exomes AF: 0.804 AC: 2525 AN: 3142 Hom.: 1034 AF XY: 0.802 AC XY: 1585 AN XY: 1976

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.676

Gnomad ASJ exome AF: 0.865

Gnomad EAS exome AF: 0.713

Gnomad SAS exome AF: 0.786

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.804 AC: 935247 AN: 1163018 Hom.: 377345 Cov.: 52 AF XY: 0.804 AC XY: 450580 AN XY: 560162

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.833 AC: 126662 AN: 152136 Hom.: 53550 Cov.: 34 AF XY: 0.829 AC XY: 61676 AN XY: 74378

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.817

Alfa AF: 0.834 Hom.: 6620

Bravo AF: 0.821

Asia WGS AF: 0.681 AC: 2360 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 -
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

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Immunodeficiency 51 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.73

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: rs917865; hg19: chr22-17565974;