chr22-17105581-C-T

Position:

• chr22-17105581-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(IL17RA):​c.932-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,610,648 control chromosomes in the GnomAD database, including 510,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51244 hom., cov: 33)
  • Exomes 𝑓: 0.79 (459740 hom.)
• Consequence: IL17RA NM_014339.7 intron
• Scores: Splicing: ADA: 0.00001350
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: -0.116

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-17105581-C-T is Benign according to our data. Variant chr22-17105581-C-T is described in ClinVar as [Benign]. Clinvar id is 340585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17105581-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.932-10C>T		intron_variant		ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.932-10C>T		intron_variant			NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.932-10C>T		intron_variant		1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.932-10C>T		intron_variant		5		ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124554 AN: 152122 Hom.: 51177 Cov.: 33

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.828

GnomAD3 exomes AF: 0.812 AC: 204298 AN: 251466 Hom.: 83399 AF XY: 0.808 AC XY: 109858 AN XY: 135910

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.894

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.820

Gnomad SAS exome AF: 0.826

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.793 AC: 1156487 AN: 1458408 Hom.: 459740 Cov.: 42 AF XY: 0.793 AC XY: 575615 AN XY: 725798

Gnomad4 AFR exome AF: 0.883

Gnomad4 AMR exome AF: 0.888

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.815

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.784

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.819 AC: 124677 AN: 152240 Hom.: 51244 Cov.: 33 AF XY: 0.816 AC XY: 60718 AN XY: 74428

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.829

Alfa AF: 0.795 Hom.: 86138

Bravo AF: 0.832

Asia WGS AF: 0.837 AC: 2906 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 51 Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
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 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Familial Candidiasis, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs2241046; hg19: chr22-17586471;