22-17084998-C-A

Variant names:

• chr22-17084998-C-A
• rs13053694
• ENST00000477874.1:n.-94C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477874.1(IL17RA):​n.-94C>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (13852 hom., cov: 32)
  • Exomes 𝑓: 0.50 (141070 hom.)
• Consequence: IL17RA ENST00000477874.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.26
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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 rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.-94C>A		upstream_gene_variant		ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-94C>A		upstream_gene_variant			NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.-94C>A		upstream_gene_variant		1	NM_014339.7	ENSP00000320936.6

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

African (AFR) AF: 0.111 AC: 2470 AN: 22290

American (AMR) AF: 0.347 AC: 2885 AN: 8314

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 8165 AN: 14686

East Asian (EAS) AF: 0.297 AC: 7754 AN: 26112

South Asian (SAS) AF: 0.434 AC: 13681 AN: 31506

European-Finnish (FIN) AF: 0.510 AC: 12542 AN: 24616

Middle Eastern (MID) AF: 0.544 AC: 2465 AN: 4534

European-Non Finnish (NFE) AF: 0.523 AC: 478220 AN: 914592

Other (OTH) AF: 0.470 AC: 20837 AN: 44374

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

African (AFR) AF: 0.127 AC: 5277 AN: 41528

American (AMR) AF: 0.375 AC: 5730 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1542 AN: 5124

South Asian (SAS) AF: 0.422 AC: 2036 AN: 4824

European-Finnish (FIN) AF: 0.493 AC: 5225 AN: 10588

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35674 AN: 67842

Other (OTH) AF: 0.431 AC: 909 AN: 2110

Alfa AF: 0.380 Hom.: 2565

Bravo AF: 0.367

Asia WGS AF: 0.319 AC: 1107 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-1.3
PromoterAI		0.013	Neutral
Mutation Taster		=300/0	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: rs13053694; hg19: chr22-17565888;