ENST00000477874.1:n.-95G>T

Variant names:

• chr22-17084859-C-T
• NM_014339.7:c.-233C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000477874.1(IL17RA):​n.-233C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL17RA ENST00000477874.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.-233C>T		upstream_gene_variant		ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-233C>T		upstream_gene_variant			NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.-233C>T		upstream_gene_variant		1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 229988 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116964

African (AFR) AF: 0.00 AC: 0 AN: 6278

American (AMR) AF: 0.00 AC: 0 AN: 6036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7992

East Asian (EAS) AF: 0.00 AC: 0 AN: 19758

South Asian (SAS) AF: 0.00 AC: 0 AN: 4268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 151976

Other (OTH) AF: 0.00 AC: 0 AN: 14548

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		0.18
PromoterAI		-0.30	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr22-17565749;