rs279545

Variant names:

• chr3-9930809-G-A
• rs279545
• NM_153460.4:c.1339-86G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9930809-G-A
• chr3-9930809-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153460.4(IL17RC):​c.1339-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,198,708 control chromosomes in the GnomAD database, including 351,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (35824 hom., cov: 33)
  • Exomes 𝑓: 0.77 (315842 hom.)
• Consequence: IL17RC NM_153460.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226
• Publications: 24 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-9930809-G-A is Benign according to our data. Variant chr3-9930809-G-A is described in ClinVar as [Benign]. Clinvar id is 2687937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4	c.1339-86G>A		intron_variant	Intron 15 of 18	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8	c.1339-86G>A		intron_variant	Intron 15 of 18	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1	n.1255-86G>A		intron_variant	Intron 14 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98316 AN: 152024 Hom.: 35813 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.771 AC: 807290 AN: 1046568 Hom.: 315842 Cov.: 15 AF XY: 0.772 AC XY: 416634 AN XY: 539714

African (AFR) AF: 0.266 AC: 6680 AN: 25084

American (AMR) AF: 0.702 AC: 31020 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 19184 AN: 23542

East Asian (EAS) AF: 0.795 AC: 30072 AN: 37844

South Asian (SAS) AF: 0.737 AC: 57341 AN: 77846

European-Finnish (FIN) AF: 0.843 AC: 44867 AN: 53196

Middle Eastern (MID) AF: 0.749 AC: 3707 AN: 4952

European-Non Finnish (NFE) AF: 0.790 AC: 579157 AN: 733302

Other (OTH) AF: 0.756 AC: 35262 AN: 46644

GnomAD4 genome AF: 0.647 AC: 98364 AN: 152140 Hom.: 35824 Cov.: 33 AF XY: 0.655 AC XY: 48700 AN XY: 74380

African (AFR) AF: 0.281 AC: 11656 AN: 41504

American (AMR) AF: 0.731 AC: 11169 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2851 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4265 AN: 5162

South Asian (SAS) AF: 0.732 AC: 3529 AN: 4822

European-Finnish (FIN) AF: 0.852 AC: 9032 AN: 10598

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53556 AN: 67988

Other (OTH) AF: 0.693 AC: 1463 AN: 2110

Alfa AF: 0.748 Hom.: 39782

Bravo AF: 0.618

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.23
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: rs279545; hg19: chr3-9972493; COSMIC: COSV55972637; COSMIC: COSV55972637;