rs879575

Variant names:

• chr22-17108677-C-T
• rs879575
• NM_014339.7:c.1458C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):​c.1458C>T​(p.Ile486Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,607,998 control chromosomes in the GnomAD database, including 41,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3323 hom., cov: 34)
  • Exomes 𝑓: 0.22 (38182 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: 1.98
• Publications: 24 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 22-17108677-C-T is Benign according to our data. Variant chr22-17108677-C-T is described in ClinVar as Benign. ClinVar VariationId is 340598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 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.1458C>T	p.Ile486Ile	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1356C>T	p.Ile452Ile	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.1458C>T	p.Ile486Ile	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1446C>T	p.Ile482Ile	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.1356C>T	p.Ile452Ile	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31020 AN: 152148 Hom.: 3324 Cov.: 34

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.193 AC: 47167 AN: 244674 AF XY: 0.197

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0510

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.224 AC: 326044 AN: 1455732 Hom.: 38182 Cov.: 62 AF XY: 0.223 AC XY: 161699 AN XY: 724526

African (AFR) AF: 0.167 AC: 5592 AN: 33466

American (AMR) AF: 0.115 AC: 5159 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6351 AN: 26120

East Asian (EAS) AF: 0.0508 AC: 2018 AN: 39690

South Asian (SAS) AF: 0.171 AC: 14789 AN: 86248

European-Finnish (FIN) AF: 0.217 AC: 10356 AN: 47748

Middle Eastern (MID) AF: 0.221 AC: 1272 AN: 5768

European-Non Finnish (NFE) AF: 0.241 AC: 267483 AN: 1111680

Other (OTH) AF: 0.216 AC: 13024 AN: 60306

GnomAD4 genome AF: 0.204 AC: 31028 AN: 152266 Hom.: 3323 Cov.: 34 AF XY: 0.201 AC XY: 14966 AN XY: 74450

African (AFR) AF: 0.169 AC: 7031 AN: 41550

American (AMR) AF: 0.158 AC: 2423 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.0576 AC: 298 AN: 5178

South Asian (SAS) AF: 0.172 AC: 833 AN: 4834

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10614

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16547 AN: 67992

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.225 Hom.: 9292

Bravo AF: 0.195

Asia WGS AF: 0.134 AC: 467 AN: 3478

EpiCase AF: 0.242

EpiControl AF: 0.244

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Familial Candidiasis, Recessive (1)
-	-	1	Immunodeficiency 51 (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		2.0
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: rs879575; hg19: chr22-17589567; COSMIC: COSV60051845;