3-9928389-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_153460.4(IL17RC):c.962C>T(p.Ser321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,604,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S321W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0210

Publications

5 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.066158324).

BS2

High AC in GnomAd4 at 23 Unknown,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.962C>T	p.Ser321Leu	missense_variant	Exon 11 of 19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8 link	c.962C>T	p.Ser321Leu	missense_variant	Exon 11 of 19	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1 link	n.878C>T		non_coding_transcript_exon_variant	Exon 10 of 24			ENSP00000507040.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

242722

AF XY:

0.0000983

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000299

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000613

AC:

AN:

1452538

Hom.:

Cov.:

AF XY:

0.0000623

AC XY:

AN XY:

721964

show subpopulations

African (AFR)

AF:

0.0000903

AC:

AN:

33206

American (AMR)

AF:

0.000343

AC:

AN:

43692

Ashkenazi Jewish (ASJ)

AF:

0.0000387

AC:

AN:

25872

East Asian (EAS)

AF:

0.000152

AC:

AN:

39542

South Asian (SAS)

AF:

0.0000932

AC:

AN:

85858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000469

AC:

AN:

1107920

Other (OTH)

AF:

0.0000666

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000151

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41580

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000107

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Uncertain:1

Jul 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 392 of the IL17RC protein (p.Ser392Leu). This variant is present in population databases (rs141178913, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with IL17RC-related conditions. ClinVar contains an entry for this variant (Variation ID: 581058). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.066

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;.;.;L;.;.;.;.;.

PhyloP100

0.021

PrimateAI

Benign

0.39

PROVEAN

Benign

0.0

.;D;D;D;.;D;D;D;D

REVEL

Benign

0.14

Sift

Pathogenic

0.0

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

Sift4G

Benign

0.10

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

Vest4

0.28

ClinPred

0.022

GERP RS

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.54

Mutation Taster

=84/16

polymorphism

(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