22-17109379-C-T

Variant names:

• chr22-17109379-C-T
• rs4819555
• NM_014339.7:c.2160C>T

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.2160C>T​(p.Pro720Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,611,270 control chromosomes in the GnomAD database, including 46,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P720P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.26 (5467 hom., cov: 34)
  • Exomes 𝑓: 0.23 (41330 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -2.91
• Publications: 12 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=-0.71).
• BP6: Variant 22-17109379-C-T is Benign according to our data. Variant chr22-17109379-C-T is described in ClinVar as Benign. ClinVar VariationId is 340608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 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.2160C>T	p.Pro720Pro	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.2058C>T	p.Pro686Pro	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.2160C>T	p.Pro720Pro	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.2148C>T	p.Pro716Pro	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.2058C>T	p.Pro686Pro	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39893 AN: 152072 Hom.: 5458 Cov.: 34

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.228 AC: 55500 AN: 243612 AF XY: 0.224

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.0756

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.234 AC: 341853 AN: 1459080 Hom.: 41330 Cov.: 38 AF XY: 0.232 AC XY: 168587 AN XY: 725756

African (AFR) AF: 0.343 AC: 11470 AN: 33456

American (AMR) AF: 0.251 AC: 11175 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6642 AN: 26084

East Asian (EAS) AF: 0.0825 AC: 3273 AN: 39674

South Asian (SAS) AF: 0.183 AC: 15709 AN: 86032

European-Finnish (FIN) AF: 0.221 AC: 11412 AN: 51698

Middle Eastern (MID) AF: 0.246 AC: 1414 AN: 5748

European-Non Finnish (NFE) AF: 0.240 AC: 266635 AN: 1111494

Other (OTH) AF: 0.234 AC: 14123 AN: 60306

GnomAD4 genome AF: 0.262 AC: 39931 AN: 152190 Hom.: 5467 Cov.: 34 AF XY: 0.259 AC XY: 19256 AN XY: 74408

African (AFR) AF: 0.338 AC: 14041 AN: 41532

American (AMR) AF: 0.258 AC: 3944 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3470

East Asian (EAS) AF: 0.0828 AC: 428 AN: 5170

South Asian (SAS) AF: 0.182 AC: 878 AN: 4828

European-Finnish (FIN) AF: 0.222 AC: 2357 AN: 10614

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16569 AN: 67952

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.211 Hom.: 1140

Bravo AF: 0.267

Asia WGS AF: 0.165 AC: 574 AN: 3478

EpiCase AF: 0.244

EpiControl AF: 0.246

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	2	not specified (2)
-	-	1	Familial Candidiasis, Recessive (1)
-	-	1	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.20
DANN	Benign	0.70
PhyloP100		-2.9
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: rs4819555; hg19: chr22-17590269; COSMIC: COSV60051494;