3-9928437-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153460.4(IL17RC):c.1010C>T(p.Pro337Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,607,348 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. P337S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.029 ( 61 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1049 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.794

Publications

9 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=0.008392245).

BP6

Variant 3-9928437-C-T is Benign according to our data. Variant chr3-9928437-C-T is described in ClinVar as Benign. ClinVar VariationId is 475919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0293 (4465/152326) while in subpopulation NFE AF = 0.0385 (2621/68020). AF 95% confidence interval is 0.0373. There are 61 homozygotes in GnomAd4. There are 2082 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 4465 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.1010C>T	p.Pro337Leu	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.1010C>T	p.Pro337Leu	missense_variant	Exon 11 of 19	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1 link	n.926C>T		non_coding_transcript_exon_variant	Exon 10 of 24			ENSP00000507040.1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4465

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.0252

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0256

AC:

6242

AN:

243830

AF XY:

0.0250

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0354

AC:

51562

AN:

1455022

Hom.:

1049

Cov.:

AF XY:

0.0344

AC XY:

24938

AN XY:

724034

show subpopulations

African (AFR)

AF:

0.0263

AC:

876

AN:

33330

American (AMR)

AF:

0.0160

AC:

707

AN:

44116

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

421

AN:

26034

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.00752

AC:

648

AN:

86154

European-Finnish (FIN)

AF:

0.0302

AC:

1472

AN:

48734

Middle Eastern (MID)

AF:

0.00992

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0408

AC:

45369

AN:

1111006

Other (OTH)

AF:

0.0334

AC:

2011

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2844

5689

8533

11378

14222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1642

3284

4926

6568

8210

<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:

0.0293

AC:

4465

AN:

152326

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2082

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0263

AC:

1092

AN:

41590

American (AMR)

AF:

0.0216

AC:

330

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00664

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0252

AC:

268

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0385

AC:

2621

AN:

68020

Other (OTH)

AF:

0.0250

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

226

452

677

903

1129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0321

Hom.:

145

Bravo

AF:

0.0292

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0506

AC:

195

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.0377

AC:

324

ExAC

AF:

0.0256

AC:

3106

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0364

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

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

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

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

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.85

T;.;D;D;D;D;D;T;D

MetaRNN

Benign

0.0084

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

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

PhyloP100

0.79

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

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

REVEL

Benign

0.11

Sift

Benign

0.33

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

Sift4G

Benign

0.87

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

Polyphen

0.015, 0.80, 0.0090

.;B;.;P;B;.;B;.;.

Vest4

0.19

MPC

0.24

ClinPred

0.0086

GERP RS

2.7

Varity_R

0.22

gMVP

0.52

Mutation Taster

=83/17

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