22-17107415-T-A

Variant names:

• chr22-17107415-T-A
• rs879574
• NM_014339.7:c.1046-312T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014339.7(IL17RA):​c.1046-312T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,184 control chromosomes in the GnomAD database, including 4,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4693 hom., cov: 33)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.1046-312T>A		intron	N/A	NP_055154.3
	IL17RA	NM_001289905.2		c.944-312T>A		intron	N/A	NP_001276834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.1046-312T>A		intron	N/A	ENSP00000320936.6
	IL17RA	ENST00000612619.2	TSL:5	c.944-312T>A		intron	N/A	ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32220 AN: 152066 Hom.: 4680 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32273 AN: 152184 Hom.: 4693 Cov.: 33 AF XY: 0.209 AC XY: 15558 AN XY: 74396

African (AFR) AF: 0.405 AC: 16809 AN: 41476

American (AMR) AF: 0.231 AC: 3533 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.0288 AC: 149 AN: 5182

South Asian (SAS) AF: 0.127 AC: 611 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1350 AN: 10606

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8378 AN: 68008

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.0806 Hom.: 120

Bravo AF: 0.229

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.60
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs879574; hg19: chr22-17588305;