rs879576

Positions:

• chr22-17108356-G-A
• chr22-17108356-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):​c.1137G>A​(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,960 control chromosomes in the GnomAD database, including 12,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1892 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10907 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.31

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 22-17108356-G-A is Benign according to our data. Variant chr22-17108356-G-A is described in ClinVar as [Benign]. Clinvar id is 340592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17108356-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1137G>A	p.Lys379Lys	synonymous_variant	13/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.1035G>A	p.Lys345Lys	synonymous_variant	12/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1137G>A	p.Lys379Lys	synonymous_variant	13/13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.1035G>A	p.Lys345Lys	synonymous_variant	12/12	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22154 AN: 152056 Hom.: 1890 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.114 AC: 28544 AN: 251174 Hom.: 2027 AF XY: 0.115 AC XY: 15649 AN XY: 135786

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0759

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.116 AC: 169645 AN: 1461784 Hom.: 10907 Cov.: 54 AF XY: 0.117 AC XY: 84805 AN XY: 727198

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.0798

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.146 AC: 22171 AN: 152176 Hom.: 1892 Cov.: 33 AF XY: 0.144 AC XY: 10679 AN XY: 74394

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.150

Alfa AF: 0.118 Hom.: 1261

Bravo AF: 0.150

Asia WGS AF: 0.0580 AC: 202 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.126

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Familial Candidiasis, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Immunodeficiency 51 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.9
DANN	Benign	0.60

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: rs879576; hg19: chr22-17589246;