22-17108319-C-T

Variant names:

• chr22-17108319-C-T
• rs879577
• NM_014339.7:c.1100C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(IL17RA):​c.1100C>T​(p.Ala367Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,456 control chromosomes in the GnomAD database, including 51,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A367E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.29 (7158 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44627 hom.)
• Consequence: IL17RA NM_014339.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -2.02
• Publications: 50 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.296137E-4).
• BP6: Variant 22-17108319-C-T is Benign according to our data. Variant chr22-17108319-C-T is described in ClinVar as Benign. ClinVar VariationId is 340591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 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.1100C>T	p.Ala367Val	missense	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.998C>T	p.Ala333Val	missense	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.1100C>T	p.Ala367Val	missense	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1088C>T	p.Ala363Val	missense	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.998C>T	p.Ala333Val	missense	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44622 AN: 151912 Hom.: 7138 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.241 AC: 60286 AN: 250576 AF XY: 0.235

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.0765

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.242 AC: 353772 AN: 1461426 Hom.: 44627 Cov.: 37 AF XY: 0.240 AC XY: 174369 AN XY: 727030

African (AFR) AF: 0.434 AC: 14536 AN: 33470

American (AMR) AF: 0.261 AC: 11656 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6551 AN: 26136

East Asian (EAS) AF: 0.0830 AC: 3296 AN: 39696

South Asian (SAS) AF: 0.194 AC: 16760 AN: 86236

European-Finnish (FIN) AF: 0.234 AC: 12476 AN: 53338

Middle Eastern (MID) AF: 0.255 AC: 1466 AN: 5742

European-Non Finnish (NFE) AF: 0.245 AC: 272257 AN: 1111740

Other (OTH) AF: 0.245 AC: 14774 AN: 60376

GnomAD4 genome AF: 0.294 AC: 44681 AN: 152030 Hom.: 7158 Cov.: 33 AF XY: 0.290 AC XY: 21542 AN XY: 74314

African (AFR) AF: 0.432 AC: 17891 AN: 41434

American (AMR) AF: 0.274 AC: 4187 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.0838 AC: 433 AN: 5170

South Asian (SAS) AF: 0.195 AC: 940 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2515 AN: 10590

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16947 AN: 67952

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.255 Hom.: 20768

Bravo AF: 0.300

TwinsUK AF: 0.242 AC: 896

ALSPAC AF: 0.255 AC: 982

ESP6500AA AF: 0.428 AC: 1884

ESP6500EA AF: 0.246 AC: 2115

ExAC AF: 0.244 AC: 29690

Asia WGS AF: 0.181 AC: 628 AN: 3478

EpiCase AF: 0.248

EpiControl AF: 0.250

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
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.010
DANN	Benign	0.79
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.00033	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	L
PhyloP100		-2.0
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.023
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.026	B
Vest4		0.012
MPC		0.19
ClinPred		0.0014	T
GERP RS		-1.4
Varity_R		0.013
gMVP		0.16
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs879577; hg19: chr22-17589209; COSMIC: COSV60051596;