rs148575246

Positions:

chr3-9932859-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 6P and 12B. PVS1_ModeratePP3_StrongBP6_Very_StrongBS2

The NM_153460.4(IL17RC):c.1522+1G>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,573,836 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 5 hom., cov: 33)

Exomes 𝑓: 0.011 ( 113 hom. )

Consequence

IL17RC
NM_153460.4 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

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

Conservation

PhyloP100: 1.10

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.017568192 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 3-9932859-G-C is Benign according to our data. Variant chr3-9932859-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 542537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.1522+1G>C		splice_donor_variant		ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8 linkuse as main transcript	c.1522+1G>C		splice_donor_variant		1	NM_153460.4	P4	Q8NAC3-2

Frequencies

GnomAD3 genomes

AF:

0.00750

AC:

1142

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00630

AC:

1285

AN:

204104

Hom.:

AF XY:

0.00625

AC XY:

701

AN XY:

112080

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00460

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.0111

AC:

15768

AN:

1421486

Hom.:

113

Cov.:

AF XY:

0.0108

AC XY:

7590

AN XY:

705180

show subpopulations

Gnomad4 AFR exome

AF:

0.00211

Gnomad4 AMR exome

AF:

0.00450

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00190

Gnomad4 FIN exome

AF:

0.00463

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00749

AC:

1141

AN:

152350

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

489

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00724

Hom.:

Bravo

AF:

0.00713

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00300

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00573

AC:

689

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 12, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Oct 06, 2020	- -

IL17RC-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

IL17RC: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.84

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.63

MutationTaster

Benign

1.0

D;D;D;D;D;D

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.97

Position offset: -1

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