rs6518660

Variant names:

• chr22-17094910-A-G
• rs6518660
• NM_014339.7:c.139-2152A>G

Variant summary

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

The NM_014339.7(IL17RA):​c.139-2152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,152 control chromosomes in the GnomAD database, including 2,329 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 0.17 (2329 hom., cov: 29)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.139-2152A>G		intron_variant	Intron 1 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.139-2152A>G		intron_variant	Intron 1 of 11		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.139-2152A>G		intron_variant	Intron 1 of 12	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25977 AN: 151040 Hom.: 2324 Cov.: 29

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26000 AN: 151152 Hom.: 2329 Cov.: 29 AF XY: 0.172 AC XY: 12658 AN XY: 73782

African (AFR) AF: 0.220 AC: 9060 AN: 41102

American (AMR) AF: 0.122 AC: 1854 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1006 AN: 5100

South Asian (SAS) AF: 0.246 AC: 1175 AN: 4774

European-Finnish (FIN) AF: 0.127 AC: 1320 AN: 10394

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.151 AC: 10233 AN: 67872

Other (OTH) AF: 0.178 AC: 373 AN: 2090

Alfa AF: 0.157 Hom.: 2448

Bravo AF: 0.170

Asia WGS AF: 0.190 AC: 655 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		0.0080
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: rs6518660; hg19: chr22-17575800;