rs882643

Variant names:

• chr22-17110933-C-G
• rs882643
• NM_014339.7:c.*1113C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(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 NM_014339.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.374
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 51

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014339.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.*1113C>G		3_prime_UTR	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.*1113C>G		3_prime_UTR	Exon 12 of 12	NP_001276834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.*1113C>G		3_prime_UTR	Exon 13 of 13	ENSP00000320936.6

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.133 AC: 4 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.177 AC: 29 AN: 164

Other (OTH) AF: 0.286 AC: 4 AN: 14

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

African (AFR) AF: 0.0620 AC: 2575 AN: 41532

American (AMR) AF: 0.138 AC: 2111 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5182

South Asian (SAS) AF: 0.125 AC: 602 AN: 4832

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10582

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10834 AN: 67998

Other (OTH) AF: 0.101 AC: 214 AN: 2112

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs882643; hg19: chr22-17591823;