rs11719981

chr3-9928404-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153460.4(IL17RC):c.977C>T(p.Ala326Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,604,918 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A326A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.833

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043530464).
• BP6: Variant 3-9928404-C-T is Benign according to our data. Variant chr3-9928404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9928404-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4	c.977C>T	p.Ala326Val	missense_variant	11/19	ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8	c.977C>T	p.Ala326Val	missense_variant	11/19	1	NM_153460.4	P4

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00166 AC: 401 AN: 241914 Hom.: 2 AF XY: 0.00159 AC XY: 210 AN XY: 131898

Gnomad AFR exome AF: 0.000922

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000555

Gnomad SAS exome AF: 0.00284

Gnomad FIN exome AF: 0.000478

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.00223 AC: 3242 AN: 1452560 Hom.: 8 Cov.: 40 AF XY: 0.00219 AC XY: 1579 AN XY: 722320

Gnomad4 AFR exome AF: 0.000542

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.0000772

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.000624

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00228

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74508

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00141 Hom.: 0

Bravo AF: 0.00132

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00175 AC: 15

ExAC AF: 0.00168 AC: 204

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

IL17RC-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 16, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Candidiasis, familial, 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	7.0
Dann	Benign	0.75
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.82	T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.0044	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.45	T
REVEL	Benign	0.014
Sift4G	Benign	0.87	T;T;T;T;.;T;T;T;T
Polyphen		0.0090, 0.46, 0.020	.;B;.;P;B;.;B;.;.
Vest4		0.16
MVP		0.030
MPC		0.24
ClinPred		0.0030	T
GERP RS		-0.082
Varity_R		0.060
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs11719981; hg19: chr3-9970088;