rs115949142

Variant names:

• chr3-9924029-T-A
• rs115949142
• NM_153460.4:c.762+9T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153460.4(IL17RC):​c.762+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,612,906 control chromosomes in the GnomAD database, including 1,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (80 hom., cov: 31)
  • Exomes 𝑓: 0.037 (1151 hom.)
• Consequence: IL17RC NM_153460.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.823
• Publications: 4 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 (BayesDel_noAF=-0.7).
• BP6: Variant 3-9924029-T-A is Benign according to our data. Variant chr3-9924029-T-A is described in ClinVar as Benign. ClinVar VariationId is 475931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0561 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.762+9T>A		intron	N/A	NP_703190.2
	IL17RC	NM_153461.4		c.975+9T>A		intron	N/A	NP_703191.2
	IL17RC	NM_001203263.2		c.762+9T>A		intron	N/A	NP_001190192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.762+9T>A		intron	N/A	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.762+9T>A		intron	N/A	ENSP00000396064.1
	IL17RC	ENST00000383812.9	TSL:1	c.717+9T>A		intron	N/A	ENSP00000373323.4

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4122 AN: 152036 Hom.: 79 Cov.: 31

Gnomad AFR AF: 0.00650

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.0315 AC: 7875 AN: 250242 AF XY: 0.0345

Gnomad AFR exome AF: 0.00617

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0292

Gnomad NFE exome AF: 0.0349

Gnomad OTH exome AF: 0.0313

GnomAD4 exome AF: 0.0366 AC: 53406 AN: 1460752 Hom.: 1151 Cov.: 32 AF XY: 0.0377 AC XY: 27399 AN XY: 726726

African (AFR) AF: 0.00475 AC: 159 AN: 33480

American (AMR) AF: 0.0150 AC: 670 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 1284 AN: 26132

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39700

South Asian (SAS) AF: 0.0668 AC: 5760 AN: 86254

European-Finnish (FIN) AF: 0.0297 AC: 1554 AN: 52334

Middle Eastern (MID) AF: 0.0425 AC: 245 AN: 5766

European-Non Finnish (NFE) AF: 0.0375 AC: 41670 AN: 1111976

Other (OTH) AF: 0.0339 AC: 2048 AN: 60392

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152154 Hom.: 80 Cov.: 31 AF XY: 0.0276 AC XY: 2055 AN XY: 74382

African (AFR) AF: 0.00648 AC: 269 AN: 41508

American (AMR) AF: 0.0224 AC: 343 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3468

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5166

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4816

European-Finnish (FIN) AF: 0.0307 AC: 325 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0380 AC: 2584 AN: 67988

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0349 Hom.: 31

Bravo AF: 0.0239

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.4
DANN	Benign	0.86
PhyloP100		-0.82
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	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: rs115949142; hg19: chr3-9965713;