rs138985119

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153460.4(IL17RC):c.161T>C(p.Val54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,640 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V54M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 13 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

Publications

4 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004909426).

BP6

Variant 3-9917956-T-C is Benign according to our data. Variant chr3-9917956-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 475929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 323 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.161T>C	p.Val54Ala	missense_variant	Exon 3 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.161T>C	p.Val54Ala	missense_variant	Exon 3 of 19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 link	n.161T>C		non_coding_transcript_exon_variant	Exon 3 of 24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00181

AC:

450

AN:

248814

AF XY:

0.00191

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000424

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00304

AC:

4444

AN:

1461322

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2145

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33480

American (AMR)

AF:

0.00177

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000568

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000303

AC:

AN:

52870

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00372

AC:

4132

AN:

1111996

Other (OTH)

AF:

0.00248

AC:

150

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

272

544

815

1087

1359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00212

AC:

323

AN:

152318

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41574

American (AMR)

AF:

0.00386

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00325

AC:

221

AN:

68018

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00285

Hom.:

Bravo

AF:

0.00226

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00187

AC:

227

EpiCase

AF:

0.00365

EpiControl

AF:

0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL17RC: BP4 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

IL17RC-related disorder

Benign:1

Jan 02, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.0

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.11

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.48

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

M_CAP

Benign

0.012

MetaRNN

Benign

0.0049

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

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

PhyloP100

-0.15

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

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

REVEL

Benign

0.036

Sift

Benign

0.38

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

Sift4G

Benign

0.33

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

Polyphen

0.013, 0.049, 0.043

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

Vest4

0.15

MVP

0.040

MPC

0.29

ClinPred

0.0052

GERP RS

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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