NM_153460.4:c.332C>T

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.332C>T(p.Ser111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,607,902 control chromosomes in the GnomAD database, including 215,790 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 (★★).

Frequency

Genomes: 𝑓 0.50 ( 19856 hom., cov: 32)

Exomes 𝑓: 0.51 ( 195934 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.702

Publications

69 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=1.642684E-5).

BP6

Variant 3-9918386-C-T is Benign according to our data. Variant chr3-9918386-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.332C>T	p.Ser111Leu	missense_variant	Exon 4 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.332C>T	p.Ser111Leu	missense_variant	Exon 4 of 19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 link	n.332C>T		non_coding_transcript_exon_variant	Exon 4 of 24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76339

AN:

151956

Hom.:

19821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.0869

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.587

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.463

AC:

111494

AN:

240610

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.0816

Gnomad FIN exome

AF:

0.588

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.511

AC:

743368

AN:

1455828

Hom.:

195934

Cov.:

AF XY:

0.507

AC XY:

367126

AN XY:

723878

show subpopulations

African (AFR)

AF:

0.480

AC:

16018

AN:

33368

American (AMR)

AF:

0.439

AC:

19197

AN:

43716

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11924

AN:

25964

East Asian (EAS)

AF:

0.0819

AC:

3240

AN:

39550

South Asian (SAS)

AF:

0.357

AC:

30581

AN:

85576

European-Finnish (FIN)

AF:

0.578

AC:

30689

AN:

53086

Middle Eastern (MID)

AF:

0.534

AC:

3045

AN:

5706

European-Non Finnish (NFE)

AF:

0.540

AC:

598767

AN:

1108702

Other (OTH)

AF:

0.497

AC:

29907

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17652

35304

52957

70609

88261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16642

33284

49926

66568

83210

<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:

0.503

AC:

76420

AN:

152074

Hom.:

19856

Cov.:

AF XY:

0.499

AC XY:

37090

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.488

AC:

20256

AN:

41482

American (AMR)

AF:

0.490

AC:

7498

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1583

AN:

3472

East Asian (EAS)

AF:

0.0863

AC:

446

AN:

5166

South Asian (SAS)

AF:

0.340

AC:

1639

AN:

4824

European-Finnish (FIN)

AF:

0.587

AC:

6210

AN:

10588

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.545

AC:

37007

AN:

67944

Other (OTH)

AF:

0.504

AC:

1063

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1927

3853

5780

7706

9633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.507

Hom.:

30898

Bravo

AF:

0.495

TwinsUK

AF:

0.538

AC:

1995

ALSPAC

AF:

0.524

AC:

2021

ESP6500AA

AF:

0.488

AC:

2150

ESP6500EA

AF:

0.532

AC:

4574

ExAC

AF:

0.460

AC:

55778

Asia WGS

AF:

0.297

AC:

1028

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.2

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.056

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.61

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

MetaRNN

Benign

0.000016

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.46

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

PhyloP100

-0.70

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.0040

Sift

Benign

0.12

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

Sift4G

Benign

0.11

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

Polyphen

0.0, 0.094, 0.043

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

Vest4

0.047

MPC

0.21

ClinPred

0.022

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.25

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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