NM_014339.7:c.-8G>C

Variant names:

• chr22-17085084-G-C
• rs917865
• NM_014339.7:c.-8G>C

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.-8G>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 1,315,154 control chromosomes in the GnomAD database, including 430,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53550 hom., cov: 34)
  • Exomes 𝑓: 0.80 (377345 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.04

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=-0.86).
• BP6: Variant 22-17085084-G-C is Benign according to our data. Variant chr22-17085084-G-C is described in ClinVar as [Benign]. Clinvar id is 340561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17085084-G-C is described in Lovd as [Benign].
• 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.-8G>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.-8G>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	c.-8G>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126564 AN: 152026 Hom.: 53500 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.818

GnomAD3 exomes AF: 0.804 AC: 2525 AN: 3142 Hom.: 1034 AF XY: 0.802 AC XY: 1585 AN XY: 1976

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.676

Gnomad ASJ exome AF: 0.865

Gnomad EAS exome AF: 0.713

Gnomad SAS exome AF: 0.786

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.804 AC: 935247 AN: 1163018 Hom.: 377345 Cov.: 52 AF XY: 0.804 AC XY: 450580 AN XY: 560162

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.833 AC: 126662 AN: 152136 Hom.: 53550 Cov.: 34 AF XY: 0.829 AC XY: 61676 AN XY: 74378

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.817

Alfa AF: 0.834 Hom.: 6620

Bravo AF: 0.821

Asia WGS AF: 0.681 AC: 2360 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Familial Candidiasis, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 51 Benign:1

Aug 19, 2021

Genome-Nilou Lab

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	-0.86
CADD	Benign	9.0
DANN	Benign	0.73

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: rs917865; hg19: chr22-17565974;