3-9918069-G-A

Variant names:

• chr3-9918069-G-A
• rs143412184
• NM_153460.4:c.274G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_153460.4(IL17RC):​c.274G>A​(p.Val92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,576,478 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V92L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (9 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:3
• Conservation: PhyloP100: 1.41
• Publications: 8 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057941675).
• BP6: Variant 3-9918069-G-A is Benign according to our data. Variant chr3-9918069-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 542544.
• BS2: High AC in GnomAd4 at 284 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.274G>A	p.Val92Met	missense	Exon 3 of 19	NP_703190.2
	IL17RC	NM_153461.4		c.487G>A	p.Val163Met	missense	Exon 3 of 19	NP_703191.2
	IL17RC	NM_001203263.2		c.274G>A	p.Val92Met	missense	Exon 3 of 18	NP_001190192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.274G>A	p.Val92Met	missense	Exon 3 of 19	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.274G>A	p.Val92Met	missense	Exon 3 of 18	ENSP00000396064.1
	IL17RC	ENST00000383812.9	TSL:1	c.274G>A	p.Val92Met	missense	Exon 3 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00188 AC: 353 AN: 187822 AF XY: 0.00201

Gnomad AFR exome AF: 0.000709

Gnomad AMR exome AF: 0.000111

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00187

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00277 AC: 3951 AN: 1424142 Hom.: 9 Cov.: 33 AF XY: 0.00272 AC XY: 1919 AN XY: 705348

African (AFR) AF: 0.000555 AC: 18 AN: 32432

American (AMR) AF: 0.000235 AC: 9 AN: 38258

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25456

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37228

South Asian (SAS) AF: 0.000987 AC: 81 AN: 82084

European-Finnish (FIN) AF: 0.00182 AC: 93 AN: 50984

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5732

European-Non Finnish (NFE) AF: 0.00330 AC: 3607 AN: 1092966

Other (OTH) AF: 0.00232 AC: 137 AN: 59002

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00166 AC XY: 124 AN XY: 74490

African (AFR) AF: 0.000986 AC: 41 AN: 41576

American (AMR) AF: 0.000523 AC: 8 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00295 AC: 201 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00249 Hom.: 3

Bravo AF: 0.00176

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.00172 AC: 207

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.49
MVP		0.13
MPC		0.77
ClinPred		0.015	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.33
Mutation Taster		=89/11	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: rs143412184; hg19: chr3-9959753;