rs11719981

Positions:

chr3-9928404-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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 (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.833

Variant links:

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 links:

IL17RC (HGNC:):

IL17RC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars. Variant chr3-9928404-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.977C>T	p.Ala326Val	missense_variant	11/19	ENST00000403601.8	NP_703190.2	Q8NAC3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8 linkuse as main transcript	c.977C>T	p.Ala326Val	missense_variant	11/19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 linkuse as main transcript	n.893C>T		non_coding_transcript_exon_variant	10/24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152242

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00159

AC XY:

210

AN XY:

131898

show subpopulations

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.:

Cov.:

AF XY:

0.00219

AC XY:

1579

AN XY:

722320

show subpopulations

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.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74508

show subpopulations

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.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00168

AC:

204

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

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, no assertion criteria provided

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.0

DANN

Benign

0.75

DEOGEN2

Benign

0.023

.;.;.;T;.;.;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.82

T;.;T;T;T;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0044

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.46

.;.;.;N;.;.;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.33

.;N;N;N;.;N;N;N;N

REVEL

Benign

0.014

Sift

Benign

0.66

.;T;T;T;.;T;T;T;T

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over