ENST00000940705.1:c.-126C>G

Variant names:

• chr22-17084966-C-G
• rs562165706
• ENST00000940705.1:c.-126C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000940705.1(IL17RA):​c.-126C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,147,760 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: IL17RA ENST00000940705.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 22-17084966-C-G is Benign according to our data. Variant chr22-17084966-C-G is described in ClinVar as Benign. ClinVar VariationId is 340554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00544 (828/152286) while in subpopulation AFR AF = 0.0188 (781/41578). AF 95% confidence interval is 0.0177. There are 5 homozygotes in GnomAd4. There are 381 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000940705.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	NM_014339.7	MANE Select	c.-126C>G		upstream_gene	N/A	NP_055154.3
	IL17RA	NM_001289905.2		c.-126C>G		upstream_gene	N/A	NP_001276834.1	Q96F46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000940705.1		c.-126C>G		5_prime_UTR	Exon 1 of 12	ENSP00000610764.1
	IL17RA	ENST00000962147.1		c.-126C>G		5_prime_UTR	Exon 1 of 10	ENSP00000632206.1
	IL17RA	ENST00000477874.1	TSL:3	n.-126C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000511612.1	A0A8Q3WKC6

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 819 AN: 152170 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000456 AC: 454 AN: 995474 Hom.: 1 Cov.: 14 AF XY: 0.000408 AC XY: 195 AN XY: 477580

African (AFR) AF: 0.0188 AC: 381 AN: 20300

American (AMR) AF: 0.00147 AC: 12 AN: 8172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14024

East Asian (EAS) AF: 0.00 AC: 0 AN: 25604

South Asian (SAS) AF: 0.0000351 AC: 1 AN: 28506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24570

Middle Eastern (MID) AF: 0.000239 AC: 1 AN: 4188

European-Non Finnish (NFE) AF: 0.0000121 AC: 10 AN: 828930

Other (OTH) AF: 0.00119 AC: 49 AN: 41180

GnomAD4 genome AF: 0.00544 AC: 828 AN: 152286 Hom.: 5 Cov.: 32 AF XY: 0.00512 AC XY: 381 AN XY: 74464

African (AFR) AF: 0.0188 AC: 781 AN: 41578

American (AMR) AF: 0.00203 AC: 31 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.00598

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.15
DANN	Benign	0.73
PhyloP100		-1.5
PromoterAI		0.036	Neutral

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: rs562165706; hg19: chr22-17565856;