22-17085086-C-T

Variant names:

• chr22-17085086-C-T
• rs922730539
• NM_014339.7:c.-6C>T

Variant summary

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

The NM_014339.7(IL17RA):​c.-6C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000858 in 1,165,574 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_014339.7	c.-6C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12		NP_001276834.1
IL17RA	NM_001289905.2	c.-6C>T		5_prime_UTR_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.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000319363.11	c.-6C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.58e-7 AC: 1 AN: 1165574 Hom.: 0 Cov.: 58 AF XY: 0.00000178 AC XY: 1 AN XY: 561606

African (AFR) AF: 0.00 AC: 0 AN: 23418

American (AMR) AF: 0.00 AC: 0 AN: 9026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15784

East Asian (EAS) AF: 0.00 AC: 0 AN: 26898

South Asian (SAS) AF: 0.00 AC: 0 AN: 44330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 966662

Other (OTH) AF: 0.0000211 AC: 1 AN: 47418

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.1
DANN	Benign	0.96
PhyloP100		-1.5
PromoterAI		-0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs922730539; hg19: chr22-17565976;