3-9928397-G-A

Variant names:

• chr3-9928397-G-A
• rs115461448
• NM_153460.4:c.970G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153460.4(IL17RC):​c.970G>A​(p.Ala324Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0141 in 1,604,258 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.014 (184 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.71
• Publications: 10 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=0.0069948733).
• BP6: Variant 3-9928397-G-A is Benign according to our data. Variant chr3-9928397-G-A is described in ClinVar as Benign. ClinVar VariationId is 475918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0118 (1805/152378) while in subpopulation SAS AF = 0.0184 (89/4832). AF 95% confidence interval is 0.0153. There are 21 homozygotes in GnomAd4. There are 931 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1805 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	NM_153460.4	MANE Select	c.970G>A	p.Ala324Thr	missense	Exon 11 of 19	NP_703190.2
	IL17RC	NM_153461.4		c.1183G>A	p.Ala395Thr	missense	Exon 11 of 19	NP_703191.2
	IL17RC	NM_001203263.2		c.970G>A	p.Ala324Thr	missense	Exon 11 of 18	NP_001190192.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.970G>A	p.Ala324Thr	missense	Exon 11 of 19	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.970G>A	p.Ala324Thr	missense	Exon 11 of 18	ENSP00000396064.1
	IL17RC	ENST00000383812.9	TSL:1	c.925G>A	p.Ala309Thr	missense	Exon 10 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1799 AN: 152260 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0121 AC: 2921 AN: 241526 AF XY: 0.0125

Gnomad AFR exome AF: 0.00506

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00465

Gnomad EAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0144 AC: 20891 AN: 1451880 Hom.: 184 Cov.: 41 AF XY: 0.0144 AC XY: 10428 AN XY: 721828

African (AFR) AF: 0.00398 AC: 132 AN: 33182

American (AMR) AF: 0.0107 AC: 464 AN: 43526

Ashkenazi Jewish (ASJ) AF: 0.00514 AC: 133 AN: 25876

East Asian (EAS) AF: 0.00159 AC: 63 AN: 39556

South Asian (SAS) AF: 0.0168 AC: 1440 AN: 85820

European-Finnish (FIN) AF: 0.0120 AC: 596 AN: 49854

Middle Eastern (MID) AF: 0.00664 AC: 38 AN: 5722

European-Non Finnish (NFE) AF: 0.0156 AC: 17243 AN: 1108324

Other (OTH) AF: 0.0130 AC: 782 AN: 60020

GnomAD4 genome AF: 0.0118 AC: 1805 AN: 152378 Hom.: 21 Cov.: 33 AF XY: 0.0125 AC XY: 931 AN XY: 74516

African (AFR) AF: 0.00459 AC: 191 AN: 41592

American (AMR) AF: 0.0165 AC: 253 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4832

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1061 AN: 68038

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0140 Hom.: 42

Bravo AF: 0.0117

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0184 AC: 71

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0172 AC: 148

ExAC AF: 0.0115 AC: 1392

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.0156

EpiControl AF: 0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Candidiasis, familial, 9 Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.091
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		0.70	P
Vest4		0.25
MPC		0.44
ClinPred		0.015	T
GERP RS		4.1
Varity_R		0.19
gMVP		0.62
Mutation Taster		=97/3	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: rs115461448; hg19: chr3-9970081;