22-17109487-C-T

Variant names:

• chr22-17109487-C-T
• rs113571926
• NM_014339.7:c.2268C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_014339.7(IL17RA):​c.2268C>T​(p.Phe756Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,610,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0930
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 22-17109487-C-T is Benign according to our data. Variant chr22-17109487-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 476363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.093 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000604 (92/152348) while in subpopulation AFR AF = 0.00207 (86/41586). AF 95% confidence interval is 0.00171. There are 0 homozygotes in GnomAd4. There are 47 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

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.2268C>T	p.Phe756Phe	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.2166C>T	p.Phe722Phe	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.2268C>T	p.Phe756Phe	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.2256C>T	p.Phe752Phe	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.2166C>T	p.Phe722Phe	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152230 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000175 AC: 42 AN: 239922 AF XY: 0.000107

Gnomad AFR exome AF: 0.00210

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000651

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000109 AC: 159 AN: 1457676 Hom.: 0 Cov.: 36 AF XY: 0.0000855 AC XY: 62 AN XY: 724800

African (AFR) AF: 0.00251 AC: 84 AN: 33434

American (AMR) AF: 0.0000451 AC: 2 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52354

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1110386

Other (OTH) AF: 0.000316 AC: 19 AN: 60214

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152348 Hom.: 0 Cov.: 34 AF XY: 0.000631 AC XY: 47 AN XY: 74496

African (AFR) AF: 0.00207 AC: 86 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000272 Hom.: 0

Bravo AF: 0.000631

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	IL17RA-related disorder (1)
-	-	1	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism

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: rs113571926; hg19: chr22-17590377;