rs2241049

Positions:

• chr22-17106790-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014339.7(IL17RA):​c.1045+836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,092 control chromosomes in the GnomAD database, including 10,805 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 0.38 (10805 hom., cov: 32)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1045+836A>G		intron_variant		ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.944-937A>G		intron_variant			NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1045+836A>G		intron_variant		1	NM_014339.7	ENSP00000320936	P2
IL17RA	ENST00000612619.2	c.944-937A>G		intron_variant		5		ENSP00000479970	A2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56973 AN: 151974 Hom.: 10784 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.375 AC: 57038 AN: 152092 Hom.: 10805 Cov.: 32 AF XY: 0.373 AC XY: 27744 AN XY: 74342

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.359

Alfa AF: 0.367 Hom.: 14352

Bravo AF: 0.383

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241049; hg19: chr22-17587680;