chr22-17108356-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014339.7(IL17RA):c.1137G>A(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,960 control chromosomes in the GnomAD database, including 12,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1892 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10907 hom. )

Consequence

IL17RA
NM_014339.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.31

Publications

24 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 22-17108356-G-A is Benign according to our data. Variant chr22-17108356-G-A is described in ClinVar as Benign. ClinVar VariationId is 340592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 13 of 13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2 link	c.1035G>A	p.Lys345Lys	synonymous_variant	Exon 12 of 12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 13 of 13	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2 link	c.1035G>A	p.Lys345Lys	synonymous_variant	Exon 12 of 12	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22154

AN:

152056

Hom.:

1890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.114

AC:

28544

AN:

251174

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.0759

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.116

AC:

169645

AN:

1461784

Hom.:

10907

Cov.:

AF XY:

0.117

AC XY:

84805

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.232

AC:

7780

AN:

33480

American (AMR)

AF:

0.0798

AC:

3570

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5970

AN:

26132

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.111

AC:

9558

AN:

86258

European-Finnish (FIN)

AF:

0.113

AC:

6016

AN:

53378

Middle Eastern (MID)

AF:

0.233

AC:

1344

AN:

5762

European-Non Finnish (NFE)

AF:

0.115

AC:

127745

AN:

1111962

Other (OTH)

AF:

0.127

AC:

7649

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

8894

17788

26682

35576

44470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4670

9340

14010

18680

23350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22171

AN:

152176

Hom.:

1892

Cov.:

AF XY:

0.144

AC XY:

10679

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.229

AC:

9506

AN:

41492

American (AMR)

AF:

0.120

AC:

1842

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

792

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.106

AC:

512

AN:

4824

European-Finnish (FIN)

AF:

0.113

AC:

1200

AN:

10598

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7887

AN:

67998

Other (OTH)

AF:

0.150

AC:

318

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

980

1960

2940

3920

4900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.121

Hom.:

1852

Bravo

AF:

0.150

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. 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

Immunodeficiency 51

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.42

CADD

Benign

6.9

(source)

DANN

Benign

0.60

PhyloP100

1.3

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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