ENST00000483582.5:c.1478G>T

Variant names:

• chr3-9932859-G-T
• rs148575246
• ENST00000483582.5:c.1478G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PP3_Strong BS2_Supporting

The ENST00000483582.5(IL17RC):​c.1478G>T​(p.Gly493Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,421,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G493A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: IL17RC ENST00000483582.5 missense
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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)

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BS2: High AC in GnomAdExome4 at 7 Unknown,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4	c.1522+1G>T		splice_donor_variant, intron_variant	Intron 18 of 18	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8	c.1522+1G>T		splice_donor_variant, intron_variant	Intron 18 of 18	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1	n.1399+156G>T		intron_variant	Intron 16 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000492 AC: 7 AN: 1421496 Hom.: 0 Cov.: 33 AF XY: 0.00000425 AC XY: 3 AN XY: 705186

African (AFR) AF: 0.0000315 AC: 1 AN: 31782

American (AMR) AF: 0.00 AC: 0 AN: 36672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 79404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00000547 AC: 6 AN: 1096300

Other (OTH) AF: 0.00 AC: 0 AN: 58474

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0	.;.;.;.;.
Eigen	Pathogenic	0.84
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.0	.;.;.;.;.
MetaRNN	Benign	0.0	.;.;.;.;.
MutationAssessor	Benign	0.0	.;.;.;.;.
PhyloP100		1.1
PROVEAN	Benign	0.0	.;.;.;.;.
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;.;.;.;.
Sift4G	Pathogenic	0.0	.;.;.;.;.
Vest4		0.0
GERP RS		4.7
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.97		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148575246; hg19: chr3-9974543;