rs3804060

Variant names:

• chr22-17109709-C-T
• rs3804060
• NM_014339.7:c.2490C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-17109709-C-T
• chr22-17109709-C-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.2490C>T​(p.Pro830Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,589,426 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (46 hom., cov: 34)
  • Exomes 𝑓: 0.0057 (211 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.06
• Publications: 3 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=-0.83).
• BP6: Variant 22-17109709-C-T is Benign according to our data. Variant chr22-17109709-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 340613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0845 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.2490C>T	p.Pro830Pro	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.2388C>T	p.Pro796Pro	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.2490C>T	p.Pro830Pro	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.2478C>T	p.Pro826Pro	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.2388C>T	p.Pro796Pro	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1394 AN: 152172 Hom.: 45 Cov.: 34

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.0154 AC: 3084 AN: 200726 AF XY: 0.0146

Gnomad AFR exome AF: 0.00435

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.0911

Gnomad FIN exome AF: 0.000519

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00785

GnomAD4 exome AF: 0.00567 AC: 8155 AN: 1437136 Hom.: 211 Cov.: 35 AF XY: 0.00594 AC XY: 4236 AN XY: 712678

African (AFR) AF: 0.00558 AC: 185 AN: 33164

American (AMR) AF: 0.0304 AC: 1231 AN: 40468

Ashkenazi Jewish (ASJ) AF: 0.000586 AC: 15 AN: 25608

East Asian (EAS) AF: 0.0809 AC: 3135 AN: 38734

South Asian (SAS) AF: 0.0206 AC: 1710 AN: 82972

European-Finnish (FIN) AF: 0.000378 AC: 19 AN: 50238

Middle Eastern (MID) AF: 0.0158 AC: 88 AN: 5570

European-Non Finnish (NFE) AF: 0.00114 AC: 1260 AN: 1100896

Other (OTH) AF: 0.00861 AC: 512 AN: 59486

GnomAD4 genome AF: 0.00918 AC: 1398 AN: 152290 Hom.: 46 Cov.: 34 AF XY: 0.0105 AC XY: 783 AN XY: 74454

African (AFR) AF: 0.00488 AC: 203 AN: 41572

American (AMR) AF: 0.0322 AC: 493 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0913 AC: 471 AN: 5160

South Asian (SAS) AF: 0.0242 AC: 117 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00123 AC: 84 AN: 68016

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00307 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.83
CADD	Benign	0.11
DANN	Benign	0.62
PhyloP100		-3.1
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: rs3804060; hg19: chr22-17590599;