rs75324888

Variant names:

• chr3-9917726-G-A
• rs75324888
• NM_153460.4:c.119G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153460.4(IL17RC):​c.119G>A​(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,613,660 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.036 (331 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (347 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.966
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011171997).
• BP6: Variant 3-9917726-G-A is Benign according to our data. Variant chr3-9917726-G-A is described in ClinVar as Benign. ClinVar VariationId is 475928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

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.119G>A	p.Arg40His	missense	Exon 2 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.332G>A	p.Arg111His	missense	Exon 2 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.119G>A	p.Arg40His	missense	Exon 2 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.119G>A	p.Arg40His	missense	Exon 2 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.119G>A	p.Arg40His	missense	Exon 2 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000383812.9	TSL:1	c.119G>A	p.Arg40His	missense	Exon 2 of 18	ENSP00000373323.4	Q8NAC3-3

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5534 AN: 152098 Hom.: 328 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0102 AC: 2520 AN: 246690 AF XY: 0.00777

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.00502

Gnomad ASJ exome AF: 0.00888

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000446

Gnomad OTH exome AF: 0.00580

GnomAD4 exome AF: 0.00399 AC: 5832 AN: 1461444 Hom.: 347 Cov.: 34 AF XY: 0.00350 AC XY: 2541 AN XY: 726984

African (AFR) AF: 0.133 AC: 4466 AN: 33470

American (AMR) AF: 0.00604 AC: 270 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00945 AC: 247 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53004

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000201 AC: 223 AN: 1111998

Other (OTH) AF: 0.00947 AC: 572 AN: 60388

GnomAD4 genome AF: 0.0364 AC: 5547 AN: 152216 Hom.: 331 Cov.: 32 AF XY: 0.0352 AC XY: 2617 AN XY: 74416

African (AFR) AF: 0.126 AC: 5241 AN: 41500

American (AMR) AF: 0.0103 AC: 158 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68016

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0150 Hom.: 255

Bravo AF: 0.0419

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.122 AC: 536

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0124 AC: 1509

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.97
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.020
Sift	Benign	0.96	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.24
MPC		0.29
ClinPred		0.0022	T
GERP RS		1.9
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.067
gMVP		0.20
Mutation Taster		=94/6	polymorphism (auto)

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: rs75324888; hg19: chr3-9959410;