chr3-9917349-C-T

Variant names:

• chr3-9917349-C-T
• rs7643547
• NM_153460.4:c.34C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_153460.4(IL17RC):​c.34C>T​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,114 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (130 hom.)
• Consequence: IL17RC NM_153460.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.438
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-9917349-C-T is Benign according to our data. Variant chr3-9917349-C-T is described in ClinVar as Benign. ClinVar VariationId is 542534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	NM_153460.4	MANE Select	c.34C>T	p.Leu12Leu	synonymous	Exon 1 of 19	NP_703190.2
	IL17RC	NM_153461.4		c.34C>T	p.Leu12Leu	synonymous	Exon 1 of 19	NP_703191.2
	IL17RC	NM_001203263.2		c.34C>T	p.Leu12Leu	synonymous	Exon 1 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.34C>T	p.Leu12Leu	synonymous	Exon 1 of 19	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.34C>T	p.Leu12Leu	synonymous	Exon 1 of 18	ENSP00000396064.1
	IL17RC	ENST00000383812.9	TSL:1	c.34C>T	p.Leu12Leu	synonymous	Exon 1 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3545 AN: 152176 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0210

GnomAD2 exomes AF: 0.00676 AC: 1696 AN: 250916 AF XY: 0.00510

Gnomad AFR exome AF: 0.0893

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.00874

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00265 AC: 3879 AN: 1461820 Hom.: 130 Cov.: 34 AF XY: 0.00234 AC XY: 1705 AN XY: 727210

African (AFR) AF: 0.0862 AC: 2886 AN: 33470

American (AMR) AF: 0.00376 AC: 168 AN: 44704

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

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

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.000147 AC: 163 AN: 1111996

Other (OTH) AF: 0.00633 AC: 382 AN: 60394

GnomAD4 genome AF: 0.0233 AC: 3549 AN: 152294 Hom.: 133 Cov.: 32 AF XY: 0.0221 AC XY: 1645 AN XY: 74468

African (AFR) AF: 0.0805 AC: 3346 AN: 41558

American (AMR) AF: 0.00627 AC: 96 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68010

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.00965 Hom.: 82

Bravo AF: 0.0271

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

IL17RC-related disorder Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Candidiasis, familial, 9 Benign:1

Jan 30, 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
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.44
PromoterAI		-0.015	Neutral
Mutation Taster		=299/1	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: rs7643547; hg19: chr3-9959033;