dbSNP rs917864: IL17RA:c.-50T>C (chr22-17085042-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53564 hom., cov: 34)

Exomes 𝑓: 0.80 ( 370753 hom. )

Consequence

IL17RA
NM_014339.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.39

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 22-17085042-T-C is Benign according to our data. Variant chr22-17085042-T-C is described in ClinVar as [Benign]. Clinvar id is 340557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 link	c.-50T>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.-50T>C		5_prime_UTR_variant	Exon 1 of 12		NP_001276834.1	Q96F46-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363 link	c.-50T>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126593

AN:

152048

Hom.:

53512

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.803

AC:

878

AN:

1094

Hom.:

354

AF XY:

0.814

AC XY:

477

AN XY:

586

show subpopulations

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 SAS exome

AF:

0.738

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.:

AF XY:

0.804

AC XY:

440659

AN XY:

548260

show subpopulations

Gnomad4 AFR exome

AF:

0.970

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.817

Gnomad4 EAS exome

AF:

0.607

Gnomad4 SAS exome

AF:

0.791

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.806

Gnomad4 OTH exome

AF:

0.800

GnomAD4 genome

AF:

0.833

AC:

126695

AN:

152164

Hom.:

53564

Cov.:

AF XY:

0.829

AC XY:

61700

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.960

Gnomad4 AMR

AF:

0.658

Gnomad4 ASJ

AF:

0.810

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.815

Gnomad4 OTH

AF:

0.817

Alfa

AF:

0.802

Hom.:

18441

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

LINK: link

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over