rs708567

Positions:

• chr3-9918386-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153460.4(IL17RC):​c.332C>T​(p.Ser111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,607,902 control chromosomes in the GnomAD database, including 215,790 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19856 hom., cov: 32)
  • Exomes 𝑓: 0.51 (195934 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.702

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.642684E-5).
• BP6: Variant 3-9918386-C-T is Benign according to our data. Variant chr3-9918386-C-T is described in ClinVar as [Benign]. Clinvar id is 1168986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4	c.332C>T	p.Ser111Leu	missense_variant	4/19	ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8	c.332C>T	p.Ser111Leu	missense_variant	4/19	1	NM_153460.4	P4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76339 AN: 151956 Hom.: 19821 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.463 AC: 111494 AN: 240610 Hom.: 27822 AF XY: 0.464 AC XY: 60319 AN XY: 130092

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.0816

Gnomad SAS exome AF: 0.352

Gnomad FIN exome AF: 0.588

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.511 AC: 743368 AN: 1455828 Hom.: 195934 Cov.: 42 AF XY: 0.507 AC XY: 367126 AN XY: 723878

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.0819

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.503 AC: 76420 AN: 152074 Hom.: 19856 Cov.: 32 AF XY: 0.499 AC XY: 37090 AN XY: 74326

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.504

Alfa AF: 0.509 Hom.: 19688

Bravo AF: 0.495

TwinsUK AF: 0.538 AC: 1995

ALSPAC AF: 0.524 AC: 2021

ESP6500AA AF: 0.488 AC: 2150

ESP6500EA AF: 0.532 AC: 4574

ExAC AF: 0.460 AC: 55778

Asia WGS AF: 0.297 AC: 1028 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Candidiasis, familial, 9 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.2
DANN	Benign	0.73
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.61	T;.;T;T;T;T;T
MetaRNN	Benign	0.000016	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.11	T;T;T;.;T;T;T
Polyphen		0.0, 0.094, 0.043	.;B;B;B;B;.;.
Vest4		0.047
MPC		0.21
ClinPred		0.022	T
GERP RS		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs708567; hg19: chr3-9960070; COSMIC: COSV55966869; COSMIC: COSV55966869;