rs143412184

Positions:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_153460.4(IL17RC):c.274G>A(p.Val92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,576,478 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 9 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.41

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057941675).

BP6

Variant 3-9918069-G-A is Benign according to our data. Variant chr3-9918069-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 542544.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.274G>A	p.Val92Met	missense_variant	3/19	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.274G>A	p.Val92Met	missense_variant	3/19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 linkuse as main transcript	n.274G>A		non_coding_transcript_exon_variant	3/24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00188

AC:

353

AN:

187822

Hom.:

AF XY:

0.00201

AC XY:

202

AN XY:

100480

show subpopulations

Gnomad AFR exome

AF:

0.000709

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000627

Gnomad FIN exome

AF:

0.00187

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00277

AC:

3951

AN:

1424142

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1919

AN XY:

705348

show subpopulations

Gnomad4 AFR exome

AF:

0.000555

Gnomad4 AMR exome

AF:

0.000235

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.0000269

Gnomad4 SAS exome

AF:

0.000987

Gnomad4 FIN exome

AF:

0.00182

Gnomad4 NFE exome

AF:

0.00330

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152336

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

124

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00267

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00172

AC:

207

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2022	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

IL17RC-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2022

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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

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

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.93

D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.0058

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;.;.;M;.;.;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

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

REVEL

Benign

0.17

Sift

Uncertain

0.0030

.;D;T;D;.;T;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;.;D;D;D;D

Polyphen

1.0, 1.0, 1.0

.;D;.;D;D;.;D;.;.

Vest4

0.49

MVP

0.13

MPC

0.77

ClinPred

0.015

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.33

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