rs5748864

Positions:

• chr22-17092051-G-A
• chr22-17092051-G-C

Variant summary

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

The NM_014339.7(IL17RA):​c.139-5011G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,026 control chromosomes in the GnomAD database, including 6,462 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 0.28 (6462 hom., cov: 32)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.139-5011G>A		intron_variant		ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.139-5011G>A		intron_variant			NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.139-5011G>A		intron_variant		1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41789 AN: 151908 Hom.: 6439 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.275 AC: 41850 AN: 152026 Hom.: 6462 Cov.: 32 AF XY: 0.276 AC XY: 20536 AN XY: 74308

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.253

Alfa AF: 0.231 Hom.: 1344

Bravo AF: 0.275

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.60

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: rs5748864; hg19: chr22-17572941;