22-17085100-C-G

Variant names:

• chr22-17085100-C-G
• rs1358603788
• NM_014339.7:c.9C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014339.7(IL17RA):​c.9C>G​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,205,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.9C>G	p.Ala3Ala	synonymous_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.9C>G	p.Ala3Ala	synonymous_variant	Exon 1 of 12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.9C>G	p.Ala3Ala	synonymous_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1205720 Hom.: 0 Cov.: 58 AF XY: 0.00000171 AC XY: 1 AN XY: 584512

African (AFR) AF: 0.00 AC: 0 AN: 24284

American (AMR) AF: 0.00 AC: 0 AN: 12118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16950

East Asian (EAS) AF: 0.00 AC: 0 AN: 27430

South Asian (SAS) AF: 0.0000376 AC: 2 AN: 53158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4826

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 988432

Other (OTH) AF: 0.00 AC: 0 AN: 49430

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.9
DANN	Benign	0.56
PhyloP100		0.11
PromoterAI		-0.12	Neutral

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: rs1358603788; hg19: chr22-17565990;