Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000403601.8(IL17RC):c.1812C>G(p.Gly604Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,605,280 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G604G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 22 hom. )

Consequence

IL17RC
ENST00000403601.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.178

Publications

1 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-9933242-C-G is Benign according to our data. Variant chr3-9933242-C-G is described in ClinVar as Benign. ClinVar VariationId is 475924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.178 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00144 (2087/1452928) while in subpopulation AMR AF = 0.0216 (950/43916). AF 95% confidence interval is 0.0205. There are 22 homozygotes in GnomAdExome4. There are 1133 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 269 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000403601.8. 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.1812C>G	p.Gly604Gly	synonymous	Exon 19 of 19	NP_703190.2
IL17RC	NM_153461.4		c.2025C>G	p.Gly675Gly	synonymous	Exon 19 of 19	NP_703191.2
IL17RC	NM_001203263.2		c.1773C>G	p.Gly591Gly	synonymous	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.1812C>G	p.Gly604Gly	synonymous	Exon 19 of 19	ENSP00000384969.3
IL17RC	ENST00000413608.2	TSL:1	c.1773C>G	p.Gly591Gly	synonymous	Exon 18 of 18	ENSP00000396064.1
IL17RC	ENST00000383812.9	TSL:1	c.1767C>G	p.Gly589Gly	synonymous	Exon 18 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00617

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00480

AC:

1092

AN:

227580

AF XY:

0.00445

show subpopulations

Gnomad AFR exome

AF:

0.000279

Gnomad AMR exome

AF:

0.0219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00574

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000605

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.00144

AC:

2087

AN:

1452928

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1133

AN XY:

722216

show subpopulations

African (AFR)

AF:

0.0000905

AC:

AN:

33138

American (AMR)

AF:

0.0216

AC:

950

AN:

43916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25780

East Asian (EAS)

AF:

0.00871

AC:

343

AN:

39398

South Asian (SAS)

AF:

0.00807

AC:

689

AN:

85396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.0000244

AC:

AN:

1108454

Other (OTH)

AF:

0.00125

AC:

AN:

59834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

123

246

368

491

614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00177

AC:

269

AN:

152352

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41588

American (AMR)

AF:

0.0111

AC:

170

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00618

AC:

AN:

5178

South Asian (SAS)

AF:

0.0110

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000225

Hom.:

Bravo

AF:

0.00255

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Candidiasis, familial, 9 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.1

(source)

DANN

Benign

0.63

PhyloP100

-0.18

Mutation Taster

=100/0

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