rs2229151

Variant names:

• chr22-17108407-G-A
• rs2229151
• NM_014339.7:c.1188G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):​c.1188G>A​(p.Leu396Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,614,048 control chromosomes in the GnomAD database, including 4,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (405 hom., cov: 34)
  • Exomes 𝑓: 0.028 (3902 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.36
• Publications: 22 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-17108407-G-A is Benign according to our data. Variant chr22-17108407-G-A is described in ClinVar as Benign. ClinVar VariationId is 340594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014339.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.1188G>A	p.Leu396Leu	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1086G>A	p.Leu362Leu	synonymous	Exon 12 of 12	NP_001276834.1	Q96F46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.1188G>A	p.Leu396Leu	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1176G>A	p.Leu392Leu	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.1086G>A	p.Leu362Leu	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4492 AN: 152196 Hom.: 406 Cov.: 34

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00454

Gnomad OTH AF: 0.0315

GnomAD2 exomes AF: 0.0757 AC: 19011 AN: 251140 AF XY: 0.0722

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.313

Gnomad FIN exome AF: 0.0396

Gnomad NFE exome AF: 0.00549

Gnomad OTH exome AF: 0.0545

GnomAD4 exome AF: 0.0279 AC: 40839 AN: 1461734 Hom.: 3902 Cov.: 62 AF XY: 0.0304 AC XY: 22117 AN XY: 727172

African (AFR) AF: 0.00299 AC: 100 AN: 33478

American (AMR) AF: 0.183 AC: 8199 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0157 AC: 409 AN: 26132

East Asian (EAS) AF: 0.290 AC: 11526 AN: 39698

South Asian (SAS) AF: 0.139 AC: 11991 AN: 86256

European-Finnish (FIN) AF: 0.0412 AC: 2194 AN: 53306

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.00354 AC: 3936 AN: 1111984

Other (OTH) AF: 0.0404 AC: 2438 AN: 60396

GnomAD4 genome AF: 0.0296 AC: 4501 AN: 152314 Hom.: 405 Cov.: 34 AF XY: 0.0350 AC XY: 2604 AN XY: 74472

African (AFR) AF: 0.00447 AC: 186 AN: 41584

American (AMR) AF: 0.0785 AC: 1201 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1558 AN: 5170

South Asian (SAS) AF: 0.146 AC: 707 AN: 4826

European-Finnish (FIN) AF: 0.0389 AC: 413 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00454 AC: 309 AN: 68030

Other (OTH) AF: 0.0345 AC: 73 AN: 2116

Alfa AF: 0.0211 Hom.: 167

Bravo AF: 0.0342

Asia WGS AF: 0.209 AC: 727 AN: 3478

EpiCase AF: 0.00333

EpiControl AF: 0.00350

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial Candidiasis, Recessive (1)
-	-	1	Immunodeficiency 51 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.79
PhyloP100		-2.4
Mutation Taster		=96/4	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: rs2229151; hg19: chr22-17589297; COSMIC: COSV60053540;