22-17100948-A-C

Variant names:

• chr22-17100948-A-C
• rs2241044
• NM_014339.7:c.550+467A>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.550+467A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,814 control chromosomes in the GnomAD database, including 16,715 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 0.47 (16715 hom., cov: 31)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.550+467A>C		intron_variant	Intron 5 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.550+467A>C		intron_variant	Intron 5 of 11		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.550+467A>C		intron_variant	Intron 5 of 12	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70730 AN: 151694 Hom.: 16691 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.466 AC: 70801 AN: 151814 Hom.: 16715 Cov.: 31 AF XY: 0.464 AC XY: 34404 AN XY: 74162

African (AFR) AF: 0.421 AC: 17432 AN: 41380

American (AMR) AF: 0.450 AC: 6870 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1601 AN: 3466

East Asian (EAS) AF: 0.287 AC: 1480 AN: 5154

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4690 AN: 10534

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34851 AN: 67902

Other (OTH) AF: 0.476 AC: 1002 AN: 2106

Alfa AF: 0.484 Hom.: 49330

Bravo AF: 0.459

Asia WGS AF: 0.379 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.65
PhyloP100		-2.5
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: rs2241044; hg19: chr22-17581838;