rs139727834

Variant names:

• chr3-9920938-C-G
• rs139727834
• NM_153460.4:c.591C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-9920938-C-G
• chr3-9920938-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_153460.4(IL17RC):​c.591C>G​(p.Leu197Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L197L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: IL17RC NM_153460.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.09
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-9920938-C-G is Benign according to our data. Variant chr3-9920938-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1988831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.09 with no splicing effect.

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.591C>G	p.Leu197Leu	synonymous	Exon 7 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.804C>G	p.Leu268Leu	synonymous	Exon 7 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.591C>G	p.Leu197Leu	synonymous	Exon 7 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.591C>G	p.Leu197Leu	synonymous	Exon 7 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.591C>G	p.Leu197Leu	synonymous	Exon 7 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000416074.6	TSL:1	c.591C>G	p.Leu197Leu	synonymous	Exon 7 of 17	ENSP00000395315.3	Q8NAC3-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453174 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722814

African (AFR) AF: 0.00 AC: 0 AN: 32980

American (AMR) AF: 0.00 AC: 0 AN: 42512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25598

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 84490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109248

Other (OTH) AF: 0.00 AC: 0 AN: 59994

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Candidiasis, familial, 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.64
DANN	Benign	0.75
PhyloP100		-5.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs139727834; hg19: chr3-9962622;