rs882643

Positions:

• chr22-17110933-C-G

Variant summary

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

The ENST00000319363.11(IL17RA):​c.*1113C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,428 control chromosomes in the GnomAD database, including 1,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1349 hom., cov: 31)
  • Exomes 𝑓: 0.17 (5 hom.)
• Consequence: IL17RA ENST00000319363.11 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.374

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=-0.87).
• BP6: Variant 22-17110933-C-G is Benign according to our data. Variant chr22-17110933-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 340638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.*1113C>G		3_prime_UTR_variant	13/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.*1113C>G		3_prime_UTR_variant	12/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.*1113C>G		3_prime_UTR_variant	13/13	1	NM_014339.7	ENSP00000320936	P2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18523 AN: 152090 Hom.: 1345 Cov.: 31

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.168 AC: 37 AN: 220 Hom.: 5 Cov.: 0 AF XY: 0.163 AC XY: 26 AN XY: 160

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.122 AC: 18539 AN: 152208 Hom.: 1349 Cov.: 31 AF XY: 0.121 AC XY: 9020 AN XY: 74414

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.101

Alfa AF: 0.140 Hom.: 201

Bravo AF: 0.116

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial Candidiasis, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.71

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: rs882643; hg19: chr22-17591823;