3-9920938-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_153460.4(IL17RC):​c.591C>T​(p.Leu197Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,605,254 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L197L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0039 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (158 hom.)
• Consequence: IL17RC NM_153460.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.09
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-9920938-C-T is Benign according to our data. Variant chr3-9920938-C-T is described in ClinVar as Benign. ClinVar VariationId is 542543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0501 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.591C>T	p.Leu197Leu	synonymous	Exon 7 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.804C>T	p.Leu268Leu	synonymous	Exon 7 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.591C>T	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>T	p.Leu197Leu	synonymous	Exon 7 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.591C>T	p.Leu197Leu	synonymous	Exon 7 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000416074.6	TSL:1	c.591C>T	p.Leu197Leu	synonymous	Exon 7 of 17	ENSP00000395315.3	Q8NAC3-7

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 591 AN: 151998 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00874 AC: 2077 AN: 237732 AF XY: 0.00983

Gnomad AFR exome AF: 0.000383

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00468

Gnomad FIN exome AF: 0.00633

Gnomad NFE exome AF: 0.000655

Gnomad OTH exome AF: 0.00404

GnomAD4 exome AF: 0.00373 AC: 5416 AN: 1453140 Hom.: 158 Cov.: 32 AF XY: 0.00488 AC XY: 3526 AN XY: 722796

African (AFR) AF: 0.000334 AC: 11 AN: 32980

American (AMR) AF: 0.0115 AC: 489 AN: 42504

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25598

East Asian (EAS) AF: 0.00230 AC: 91 AN: 39504

South Asian (SAS) AF: 0.0456 AC: 3849 AN: 84472

European-Finnish (FIN) AF: 0.00588 AC: 313 AN: 53220

Middle Eastern (MID) AF: 0.000711 AC: 4 AN: 5626

European-Non Finnish (NFE) AF: 0.000288 AC: 319 AN: 1109246

Other (OTH) AF: 0.00565 AC: 339 AN: 59990

GnomAD4 genome AF: 0.00394 AC: 599 AN: 152114 Hom.: 7 Cov.: 32 AF XY: 0.00519 AC XY: 386 AN XY: 74374

African (AFR) AF: 0.000434 AC: 18 AN: 41468

American (AMR) AF: 0.0107 AC: 163 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00580 AC: 30 AN: 5176

South Asian (SAS) AF: 0.0555 AC: 268 AN: 4826

European-Finnish (FIN) AF: 0.00681 AC: 72 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68000

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.000840 Hom.: 1

Bravo AF: 0.00269

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.69
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;