rs5748864

Variant names:

• chr22-17092051-G-A
• rs5748864
• NM_014339.7:c.139-5011G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_014339.7(IL17RA):​c.139-5011G>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
• Publications: 8 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=-0.9).
• 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 rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.139-5011G>A		intron_variant	Intron 1 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.139-5011G>A		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.139-5011G>A		intron_variant	Intron 1 of 12	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

African (AFR) AF: 0.414 AC: 17166 AN: 41444

American (AMR) AF: 0.181 AC: 2770 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2213 AN: 5148

South Asian (SAS) AF: 0.326 AC: 1567 AN: 4814

European-Finnish (FIN) AF: 0.232 AC: 2456 AN: 10590

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14024 AN: 67976

Other (OTH) AF: 0.253 AC: 534 AN: 2114

Alfa AF: 0.234 Hom.: 2813

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
PhyloP100		0.17
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: rs5748864; hg19: chr22-17572941;