NM_014339.7:c.1689C>T

Variant names:

• chr22-17108908-C-T
• rs146292661
• NM_014339.7:c.1689C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014339.7(IL17RA):​c.1689C>T​(p.Gly563Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,611,472 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.47
• Publications: 0 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=-0.73).
• BP6: Variant 22-17108908-C-T is Benign according to our data. Variant chr22-17108908-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 340603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00177 (269/152334) while in subpopulation NFE AF = 0.00251 (171/68022). AF 95% confidence interval is 0.00221. There are 0 homozygotes in GnomAd4. There are 129 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

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.1689C>T	p.Gly563Gly	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1587C>T	p.Gly529Gly	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.1689C>T	p.Gly563Gly	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1677C>T	p.Gly559Gly	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.1587C>T	p.Gly529Gly	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 269 AN: 152216 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00163

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00206 AC: 494 AN: 240352 AF XY: 0.00187

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00337

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00308

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00305

GnomAD4 exome AF: 0.00211 AC: 3073 AN: 1459138 Hom.: 3 Cov.: 45 AF XY: 0.00208 AC XY: 1509 AN XY: 725876

African (AFR) AF: 0.000299 AC: 10 AN: 33456

American (AMR) AF: 0.00220 AC: 98 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00265 AC: 69 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.000477 AC: 41 AN: 86034

European-Finnish (FIN) AF: 0.00320 AC: 167 AN: 52124

Middle Eastern (MID) AF: 0.00192 AC: 11 AN: 5742

European-Non Finnish (NFE) AF: 0.00228 AC: 2534 AN: 1111314

Other (OTH) AF: 0.00237 AC: 143 AN: 60214

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152334 Hom.: 0 Cov.: 34 AF XY: 0.00173 AC XY: 129 AN XY: 74488

African (AFR) AF: 0.000361 AC: 15 AN: 41586

American (AMR) AF: 0.00163 AC: 25 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00278 Hom.: 0

Bravo AF: 0.00166

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Immunodeficiency 51 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.82
DANN	Benign	0.57
PhyloP100		-1.5
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: rs146292661; hg19: chr22-17589798;