3-9928378-C-G

Variant names:

• chr3-9928378-C-G
• rs151110374
• NM_153460.4:c.951C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153460.4(IL17RC):​c.951C>G​(p.Asp317Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,604,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D317D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04980758).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	NM_153460.4	MANE Select	c.951C>G	p.Asp317Glu	missense	Exon 11 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.1164C>G	p.Asp388Glu	missense	Exon 11 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.951C>G	p.Asp317Glu	missense	Exon 11 of 18	NP_001190192.2	Q8NAC3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.951C>G	p.Asp317Glu	missense	Exon 11 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.951C>G	p.Asp317Glu	missense	Exon 11 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000383812.9	TSL:1	c.906C>G	p.Asp302Glu	missense	Exon 10 of 18	ENSP00000373323.4	Q8NAC3-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452446 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 721622

African (AFR) AF: 0.00 AC: 0 AN: 33242

American (AMR) AF: 0.00 AC: 0 AN: 43880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106978

Other (OTH) AF: 0.00 AC: 0 AN: 59992

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0080
DANN	Benign	0.25
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.71	N
PhyloP100		-2.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.071
Sift	Benign	0.42	T
Sift4G	Benign	0.36	T
Polyphen		0.0030	B
Vest4		0.073
MutPred		0.35		Gain of sheet (P = 0.0221)
MVP		0.048
MPC		0.22
ClinPred		0.045	T
GERP RS		-7.9
Varity_R		0.15
gMVP		0.29
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs151110374; hg19: chr3-9970062;