rs375878052

Variant names:

• chr3-9917537-G-GTCTGGTCTT
• rs375878052
• NM_153460.4:c.105+123_105+124insCTTTCTGGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_153461.4(IL17RC):​c.228_229insCTTTCTGGT​(p.Leu74_Gly76dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,614,210 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (15 hom.)
• Consequence: IL17RC NM_153461.4 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.152
• Publications: 1 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 -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_153461.4.
• BP6: Variant 3-9917537-G-GTCTGGTCTT is Benign according to our data. Variant chr3-9917537-G-GTCTGGTCTT is described in ClinVar as Benign. ClinVar VariationId is 542550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00947 (1442/152322) while in subpopulation AFR AF = 0.0332 (1379/41576). AF 95% confidence interval is 0.0317. There are 19 homozygotes in GnomAd4. There are 676 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1442 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153461.4. 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.105+123_105+124insCTTTCTGGT		intron	N/A	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.228_229insCTTTCTGGT	p.Leu74_Gly76dup	conservative_inframe_insertion	Exon 1 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.105+123_105+124insCTTTCTGGT		intron	N/A	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.105+123_105+124insCTTTCTGGT		intron	N/A	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.105+123_105+124insCTTTCTGGT		intron	N/A	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000383812.9	TSL:1	c.105+123_105+124insCTTTCTGGT		intron	N/A	ENSP00000373323.4	Q8NAC3-3

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1438 AN: 152204 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.00235 AC: 589 AN: 250886 AF XY: 0.00172

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000861 AC: 1258 AN: 1461888 Hom.: 15 Cov.: 34 AF XY: 0.000737 AC XY: 536 AN XY: 727244

African (AFR) AF: 0.0310 AC: 1038 AN: 33480

American (AMR) AF: 0.00161 AC: 72 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1112010

Other (OTH) AF: 0.00185 AC: 112 AN: 60396

GnomAD4 genome AF: 0.00947 AC: 1442 AN: 152322 Hom.: 19 Cov.: 32 AF XY: 0.00908 AC XY: 676 AN XY: 74482

African (AFR) AF: 0.0332 AC: 1379 AN: 41576

American (AMR) AF: 0.00300 AC: 46 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00457 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Candidiasis, familial, 9 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=79/21	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375878052; hg19: chr3-9959221;