rs141404925

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1768A>G(p.Ser590Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,608,422 control chromosomes in the GnomAD database, including 16 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S590R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 14 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.739

Publications

8 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=0.0065015256).

BP6

Variant 3-9933198-A-G is Benign according to our data. Variant chr3-9933198-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 542536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 252 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL17RC	NM_153460.4	MANE Select	c.1768A>G	p.Ser590Gly	missense	Exon 19 of 19	NP_703190.2
IL17RC	NM_153461.4		c.1981A>G	p.Ser661Gly	missense	Exon 19 of 19	NP_703191.2
IL17RC	NM_001203263.2		c.1729A>G	p.Ser577Gly	missense	Exon 18 of 18	NP_001190192.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.1768A>G	p.Ser590Gly	missense	Exon 19 of 19	ENSP00000384969.3
IL17RC	ENST00000413608.2	TSL:1	c.1729A>G	p.Ser577Gly	missense	Exon 18 of 18	ENSP00000396064.1
IL17RC	ENST00000383812.9	TSL:1	c.1723A>G	p.Ser575Gly	missense	Exon 18 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

252

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00192

AC:

455

AN:

237116

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.000682

Gnomad ASJ exome

AF:

0.00459

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00240

GnomAD4 exome

AF:

0.00248

AC:

3614

AN:

1456148

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1746

AN XY:

724400

show subpopulations

African (AFR)

AF:

0.000331

AC:

AN:

33264

American (AMR)

AF:

0.000725

AC:

AN:

44142

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

100

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00162

AC:

139

AN:

85660

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

51792

Middle Eastern (MID)

AF:

0.000704

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00281

AC:

3117

AN:

1110066

Other (OTH)

AF:

0.00223

AC:

134

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

230

460

690

920

1150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.00165

AC:

252

AN:

152274

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41554

American (AMR)

AF:

0.000849

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00266

AC:

181

AN:

67998

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00238

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00200

AC:

242

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Candidiasis, familial, 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.14

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.82

M_CAP

Benign

0.033

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.74

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.97

REVEL

Benign

0.027

Sift

Benign

0.25

Sift4G

Benign

0.13

Polyphen

0.11

Vest4

0.14

MVP

0.088

MPC

0.38

ClinPred

0.0043

GERP RS

2.1

Varity_R

0.071

gMVP

0.18

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over