rs138985119

Positions:

chr3-9917956-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153460.4(IL17RC):c.161T>C(p.Val54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,640 control chromosomes in the GnomAD database, including 14 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 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 13 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.148

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004909426).

BP6

Variant 3-9917956-T-C is Benign according to our data. Variant chr3-9917956-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 475929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9917956-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.161T>C	p.Val54Ala	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.161T>C	p.Val54Ala	missense_variant	3/19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 linkuse as main transcript	n.161T>C		non_coding_transcript_exon_variant	3/24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00181

AC:

450

AN:

248814

Hom.:

AF XY:

0.00191

AC XY:

257

AN XY:

134462

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000424

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00304

AC:

4444

AN:

1461322

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2145

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00212

AC:

323

AN:

152318

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00226

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00187

AC:

227

EpiCase

AF:

0.00365

EpiControl

AF:

0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	IL17RC: BP4 -

IL17RC-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 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 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.0

DANN

Benign

0.54

DEOGEN2

Benign

0.11

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.48

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

M_CAP

Benign

0.012

MetaRNN

Benign

0.0049

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

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

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

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

REVEL

Benign

0.036

Sift

Benign

0.38

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

Sift4G

Benign

0.33

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

Polyphen

0.013, 0.049, 0.043

.;B;.;B;B;.;B;.;.

Vest4

0.15

MVP

0.040

MPC

0.29

ClinPred

0.0052

GERP RS

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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