rs12159217

Variant names:

• chr22-17093025-G-T
• rs12159217
• NM_014339.7:c.139-4037G>T

Variant summary

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

The NM_014339.7(IL17RA):​c.139-4037G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,890 control chromosomes in the GnomAD database, including 954 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 0.11 (954 hom., cov: 32)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.139-4037G>T		intron_variant	Intron 1 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.139-4037G>T		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.139-4037G>T		intron_variant	Intron 1 of 12	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16469 AN: 151776 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.108 AC: 16474 AN: 151890 Hom.: 954 Cov.: 32 AF XY: 0.106 AC XY: 7895 AN XY: 74232

African (AFR) AF: 0.120 AC: 4984 AN: 41404

American (AMR) AF: 0.0723 AC: 1104 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 359 AN: 3468

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5176

South Asian (SAS) AF: 0.112 AC: 537 AN: 4808

European-Finnish (FIN) AF: 0.0930 AC: 975 AN: 10488

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8139 AN: 67966

Other (OTH) AF: 0.103 AC: 218 AN: 2108

Alfa AF: 0.114 Hom.: 883

Bravo AF: 0.107

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.60
PhyloP100		-1.0
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: rs12159217; hg19: chr22-17573915;