NM_014339.7:c.-50T>C

Variant names:

• chr22-17085042-T-C
• rs917864
• NM_014339.7:c.-50T>C

Variant summary

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

The NM_014339.7(IL17RA):​c.-50T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,296,336 control chromosomes in the GnomAD database, including 424,317 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 0.83 (53564 hom., cov: 34)
  • Exomes 𝑓: 0.80 (370753 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.39
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.-50T>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-50T>C		5_prime_UTR_variant	Exon 1 of 12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.-50T>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126593 AN: 152048 Hom.: 53512 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.818

GnomAD2 exomes AF: 0.803 AC: 878 AN: 1094 AF XY: 0.814

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 0.763

Gnomad ASJ exome AF: 0.833

Gnomad EAS exome AF: 0.662

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.804 AC: 919517 AN: 1144172 Hom.: 370753 Cov.: 32 AF XY: 0.804 AC XY: 440659 AN XY: 548260

African (AFR) AF: 0.970 AC: 22399 AN: 23102

American (AMR) AF: 0.597 AC: 5085 AN: 8520

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 12541 AN: 15342

East Asian (EAS) AF: 0.607 AC: 16136 AN: 26590

South Asian (SAS) AF: 0.791 AC: 30962 AN: 39130

European-Finnish (FIN) AF: 0.832 AC: 21816 AN: 26230

Middle Eastern (MID) AF: 0.873 AC: 4086 AN: 4680

European-Non Finnish (NFE) AF: 0.806 AC: 769281 AN: 954056

Other (OTH) AF: 0.800 AC: 37211 AN: 46522

GnomAD4 genome AF: 0.833 AC: 126695 AN: 152164 Hom.: 53564 Cov.: 34 AF XY: 0.829 AC XY: 61700 AN XY: 74398

African (AFR) AF: 0.960 AC: 39907 AN: 41558

American (AMR) AF: 0.658 AC: 10063 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2810 AN: 3468

East Asian (EAS) AF: 0.607 AC: 3110 AN: 5120

South Asian (SAS) AF: 0.765 AC: 3690 AN: 4826

European-Finnish (FIN) AF: 0.842 AC: 8944 AN: 10618

Middle Eastern (MID) AF: 0.925 AC: 270 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55387 AN: 67964

Other (OTH) AF: 0.817 AC: 1723 AN: 2110

Alfa AF: 0.805 Hom.: 22330

Bravo AF: 0.821

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -

Familial Candidiasis, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.54
PhyloP100		-1.4
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	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: rs917864; hg19: chr22-17565932;