rs75324888

Variant names:

Variant summary

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

The NM_153460.4(IL17RC):c.119G>A(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,613,660 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.036 ( 331 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 347 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.966

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011171997).

BP6

Variant 3-9917726-G-A is Benign according to our data. Variant chr3-9917726-G-A is described in ClinVar as Benign. ClinVar VariationId is 475928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.119G>A	p.Arg40His	missense_variant	Exon 2 of 19	ENST00000403601.8	NP_703190.2	Q8NAC3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8 link	c.119G>A	p.Arg40His	missense_variant	Exon 2 of 19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 link	n.119G>A		non_coding_transcript_exon_variant	Exon 2 of 24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5534

AN:

152098

Hom.:

328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0359

GnomAD2 exomes

AF:

0.0102

AC:

2520

AN:

246690

AF XY:

0.00777

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.00502

Gnomad ASJ exome

AF:

0.00888

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000446

Gnomad OTH exome

AF:

0.00580

GnomAD4 exome

AF:

0.00399

AC:

5832

AN:

1461444

Hom.:

347

Cov.:

AF XY:

0.00350

AC XY:

2541

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.133

AC:

4466

AN:

33470

American (AMR)

AF:

0.00604

AC:

270

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

247

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000174

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000201

AC:

223

AN:

1111998

Other (OTH)

AF:

0.00947

AC:

572

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

336

672

1009

1345

1681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.0364

AC:

5547

AN:

152216

Hom.:

331

Cov.:

AF XY:

0.0352

AC XY:

2617

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.126

AC:

5241

AN:

41500

American (AMR)

AF:

0.0103

AC:

158

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68016

Other (OTH)

AF:

0.0355

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

242

483

725

966

1208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0150

Hom.:

255

Bravo

AF:

0.0419

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.122

AC:

536

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0124

AC:

1509

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

IL17RC-related disorder

Benign:1

Jul 08, 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). -

Candidiasis, familial, 9

Benign:1

Jan 30, 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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.042

.;.;.;T;.;.;.;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.12

T;.;T;T;T;T;T;T;T

MetaRNN

Benign

0.0011

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.;N;.;.;.;.;.

PhyloP100

0.97

PrimateAI

Benign

0.37

PROVEAN

Benign

1.7

.;N;N;N;.;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.96

.;T;T;T;.;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.;T;T;T;T

Polyphen

0.0, 0.0010

.;B;.;B;B;.;B;.;.

Vest4

0.24

MPC

0.29

ClinPred

0.0022

GERP RS

1.9

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.067

gMVP

0.20

Mutation Taster

=94/6

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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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