rs148575246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 4P and 12B. PP3_StrongBP6_Very_StrongBS2

The ENST00000483582.5(IL17RC):c.1478G>C(p.Gly493Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,573,836 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 5 hom., cov: 33)

Exomes 𝑓: 0.011 ( 113 hom. )

Consequence

IL17RC
ENST00000483582.5 missense

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.10

Publications

8 publications found

Variant links:

Genes affected

IL17RC (HGNC:18358): (interleukin 17 receptor C) This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling. [provided by RefSeq, Feb 2011]

IL17RC Gene-Disease associations (from GenCC):

chronic mucocutaneous candidiasis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
candidiasis, familial, 9
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IL17RC links:

ENSG00000288550 (HGNC:):

ENSG00000288550 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 3-9932859-G-C is Benign according to our data. Variant chr3-9932859-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 542537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1141 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.1522+1G>C		splice_donor_variant, intron_variant	Intron 18 of 18	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8 link	c.1522+1G>C		splice_donor_variant, intron_variant	Intron 18 of 18	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1 link	n.1399+156G>C		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes

AF:

0.00750

AC:

1142

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00630

AC:

1285

AN:

204104

AF XY:

0.00625

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00460

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.0111

AC:

15768

AN:

1421486

Hom.:

113

Cov.:

AF XY:

0.0108

AC XY:

7590

AN XY:

705180

show subpopulations

African (AFR)

AF:

0.00211

AC:

AN:

31782

American (AMR)

AF:

0.00450

AC:

165

AN:

36672

Ashkenazi Jewish (ASJ)

AF:

0.00187

AC:

AN:

22966

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39530

South Asian (SAS)

AF:

0.00190

AC:

151

AN:

79404

European-Finnish (FIN)

AF:

0.00463

AC:

235

AN:

50810

Middle Eastern (MID)

AF:

0.00216

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.0132

AC:

14487

AN:

1096290

Other (OTH)

AF:

0.0104

AC:

607

AN:

58474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

894

1788

2682

3576

4470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.00749

AC:

1141

AN:

152350

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

489

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41586

American (AMR)

AF:

0.00771

AC:

118

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00186

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00471

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

855

AN:

68028

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00724

Hom.:

Bravo

AF:

0.00713

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00300

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00573

AC:

689

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Benign:3

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 06, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

IL17RC-related disorder

Benign:1

Jul 03, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL17RC: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.84

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.63

PhyloP100

1.1

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=89/11

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.97

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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