chr22-17108908-C-T

Position:

• chr22-17108908-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014339.7(IL17RA):​c.1689C>T​(p.Gly563=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 340603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17108908-C-T is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1689C>T	p.Gly563=	synonymous_variant	13/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.1587C>T	p.Gly529=	synonymous_variant	12/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1689C>T	p.Gly563=	synonymous_variant	13/13	1	NM_014339.7	ENSP00000320936	P2
IL17RA	ENST00000612619.2	c.1587C>T	p.Gly529=	synonymous_variant	12/12	5		ENSP00000479970	A2

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

GnomAD3 exomes AF: 0.00206 AC: 494 AN: 240352 Hom.: 0 AF XY: 0.00187 AC XY: 246 AN XY: 131394

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 SAS exome AF: 0.000463

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

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000477

Gnomad4 FIN exome AF: 0.00320

Gnomad4 NFE exome AF: 0.00228

Gnomad4 OTH exome AF: 0.00237

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

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00278 Hom.: 0

Bravo AF: 0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	IL17RA: BP4, BP7 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Immunodeficiency 51 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.82
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs146292661; hg19: chr22-17589798;