rs551742239

Positions:

• chr22-17109651-TGGAGGAAGA-T
• chr22-17109651-TGGAGGAAGA-TGGAGGAAGAGGAGGAAGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014339.7(IL17RA):​c.2446_2454delGAAGAGGAG​(p.Glu816_Glu818del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00124 in 1,606,872 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: IL17RA NM_014339.7 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 4.24

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 -10 ACMG points.

• BP6: Variant 22-17109651-TGGAGGAAGA-T is Benign according to our data. Variant chr22-17109651-TGGAGGAAGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 476365.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-17109651-TGGAGGAAGA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00212 (322/152058) while in subpopulation SAS AF= 0.00478 (23/4812). AF 95% confidence interval is 0.00393. There are 0 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.2446_2454delGAAGAGGAG	p.Glu816_Glu818del	conservative_inframe_deletion	13/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.2344_2352delGAAGAGGAG	p.Glu782_Glu784del	conservative_inframe_deletion	12/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.2446_2454delGAAGAGGAG	p.Glu816_Glu818del	conservative_inframe_deletion	13/13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.2344_2352delGAAGAGGAG	p.Glu782_Glu784del	conservative_inframe_deletion	12/12	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 321 AN: 151940 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00445

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00138 AC: 323 AN: 234784 Hom.: 1 AF XY: 0.00145 AC XY: 186 AN XY: 127990

Gnomad AFR exome AF: 0.00344

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00124

Gnomad EAS exome AF: 0.000511

Gnomad SAS exome AF: 0.00354

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000844

Gnomad OTH exome AF: 0.00173

GnomAD4 exome AF: 0.00115 AC: 1678 AN: 1454814 Hom.: 4 AF XY: 0.00125 AC XY: 904 AN XY: 723130

Gnomad4 AFR exome AF: 0.00410

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.00177

Gnomad4 EAS exome AF: 0.000710

Gnomad4 SAS exome AF: 0.00411

Gnomad4 FIN exome AF: 0.0000961

Gnomad4 NFE exome AF: 0.000854

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00212 AC: 322 AN: 152058 Hom.: 0 Cov.: 33 AF XY: 0.00211 AC XY: 157 AN XY: 74354

Gnomad4 AFR AF: 0.00446

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00478

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000619 Hom.: 0

Bravo AF: 0.00214

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Immunodeficiency 51 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs551742239; hg19: chr22-17590541;