chr22-17085084-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.04

Publications

10 publications found

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 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

IL17RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.-8G>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.-8G>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	ENST00000319363.11 link	c.-8G>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126564

AN:

152026

Hom.:

53500

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.804

AC:

2525

AN:

3142

AF XY:

0.802

show subpopulations

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 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.:

AF XY:

0.804

AC XY:

450580

AN XY:

560162

show subpopulations

African (AFR)

AF:

0.969

AC:

22692

AN:

23408

American (AMR)

AF:

0.599

AC:

5361

AN:

8950

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

12867

AN:

15708

East Asian (EAS)

AF:

0.607

AC:

16303

AN:

26864

South Asian (SAS)

AF:

0.795

AC:

34827

AN:

43800

European-Finnish (FIN)

AF:

0.833

AC:

22630

AN:

27176

Middle Eastern (MID)

AF:

0.873

AC:

4103

AN:

4700

European-Non Finnish (NFE)

AF:

0.807

AC:

778632

AN:

965142

Other (OTH)

AF:

0.800

AC:

37832

AN:

47270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

9833

19665

29498

39330

49163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.833

AC:

126662

AN:

152136

Hom.:

53550

Cov.:

AF XY:

0.829

AC XY:

61676

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.960

AC:

39890

AN:

41544

American (AMR)

AF:

0.658

AC:

10063

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

2811

AN:

3468

East Asian (EAS)

AF:

0.606

AC:

3107

AN:

5124

South Asian (SAS)

AF:

0.765

AC:

3690

AN:

4824

European-Finnish (FIN)

AF:

0.842

AC:

8934

AN:

10606

Middle Eastern (MID)

AF:

0.925

AC:

270

AN:

292

European-Non Finnish (NFE)

AF:

0.815

AC:

55381

AN:

67958

Other (OTH)

AF:

0.817

AC:

1725

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1041

2083

3124

4166

5207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

LINK: link

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

(source)

DANN

Benign

0.73

PhyloP100

1.0

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

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chr22-17085084-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over