rs75692599

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.640G>A(p.Val214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,614,080 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 31)

Exomes 𝑓: 0.016 ( 220 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

Publications

12 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=0.0050364435).

BP6

Variant 3-9923898-G-A is Benign according to our data. Variant chr3-9923898-G-A is described in ClinVar as Benign. ClinVar VariationId is 475930.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 = 0.0121 (1841/152294) while in subpopulation NFE AF = 0.0184 (1252/68014). AF 95% confidence interval is 0.0176. There are 18 homozygotes in GnomAd4. There are 869 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1841 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4 link	c.640G>A	p.Val214Met	missense_variant	Exon 8 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.640G>A	p.Val214Met	missense_variant	Exon 8 of 19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 link	n.595G>A		non_coding_transcript_exon_variant	Exon 7 of 24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1838

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0142

AC:

3565

AN:

251464

AF XY:

0.0142

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00963

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.0161

AC:

23547

AN:

1461786

Hom.:

220

Cov.:

AF XY:

0.0160

AC XY:

11615

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00254

AC:

AN:

33474

American (AMR)

AF:

0.00977

AC:

437

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

647

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00667

AC:

575

AN:

86254

European-Finnish (FIN)

AF:

0.0168

AC:

897

AN:

53408

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0179

AC:

19870

AN:

1111960

Other (OTH)

AF:

0.0155

AC:

936

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1277

2554

3831

5108

6385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.0121

AC:

1841

AN:

152294

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

869

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00339

AC:

141

AN:

41560

American (AMR)

AF:

0.00817

AC:

125

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00497

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0149

AC:

158

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0184

AC:

1252

AN:

68014

Other (OTH)

AF:

0.0132

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

192

289

385

481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0164

Hom.:

Bravo

AF:

0.0118

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0235

AC:

202

ExAC

AF:

0.0150

AC:

1824

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0209

EpiControl

AF:

0.0218

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

0.22

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

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

Eigen

Benign

0.0048

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.93

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

MetaRNN

Benign

0.0050

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

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

PhyloP100

1.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.072

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.0030

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

Polyphen

0.97, 1.0

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

Vest4

0.36

MPC

0.60

ClinPred

0.022

GERP RS

2.2

Varity_R

0.16

gMVP

0.35

Mutation Taster

=97/3

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