rs11719981

Variant names:

• chr3-9928404-C-T
• rs11719981
• NM_153460.4:c.977C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153460.4(IL17RC):​c.977C>T​(p.Ala326Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,604,918 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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. A326T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 0.833
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043530464).
• BP6: Variant 3-9928404-C-T is Benign according to our data. Variant chr3-9928404-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 542545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 193 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	NM_153460.4	MANE Select	c.977C>T	p.Ala326Val	missense	Exon 11 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.1190C>T	p.Ala397Val	missense	Exon 11 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.977C>T	p.Ala326Val	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.977C>T	p.Ala326Val	missense	Exon 11 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.977C>T	p.Ala326Val	missense	Exon 11 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000383812.9	TSL:1	c.932C>T	p.Ala311Val	missense	Exon 10 of 18	ENSP00000373323.4	Q8NAC3-3

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00166 AC: 401 AN: 241914 AF XY: 0.00159

Gnomad AFR exome AF: 0.000922

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000555

Gnomad FIN exome AF: 0.000478

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.00223 AC: 3242 AN: 1452560 Hom.: 8 Cov.: 40 AF XY: 0.00219 AC XY: 1579 AN XY: 722320

African (AFR) AF: 0.000542 AC: 18 AN: 33200

American (AMR) AF: 0.00174 AC: 76 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.0000772 AC: 2 AN: 25902

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39588

South Asian (SAS) AF: 0.00152 AC: 131 AN: 85914

European-Finnish (FIN) AF: 0.000624 AC: 31 AN: 49656

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5722

European-Non Finnish (NFE) AF: 0.00256 AC: 2841 AN: 1108960

Other (OTH) AF: 0.00228 AC: 137 AN: 60038

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74508

African (AFR) AF: 0.000866 AC: 36 AN: 41594

American (AMR) AF: 0.00118 AC: 18 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00152 Hom.: 6

Bravo AF: 0.00132

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00175 AC: 15

ExAC AF: 0.00168 AC: 204

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Candidiasis, familial, 9 (1)
-	-	1	IL17RC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.0
DANN	Benign	0.75
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.83
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.014
Sift	Benign	0.66	T
Sift4G	Benign	0.87	T
Polyphen		0.0090	B
Vest4		0.16
MVP		0.030
MPC		0.24
ClinPred		0.0030	T
GERP RS		-0.082
Varity_R		0.060
gMVP		0.37
Mutation Taster		=98/2	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: rs11719981; hg19: chr3-9970088;