3-9928347-A-G

Position:

chr3-9928347-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153460.4(IL17RC):c.920A>G(p.Gln307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,603,840 control chromosomes in the GnomAD database, including 792,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75524 hom., cov: 34)

Exomes 𝑓: 0.99 ( 717326 hom. )

Consequence

IL17RC
NM_153460.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.08

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.66898E-7).

BP6

Variant 3-9928347-A-G is Benign according to our data. Variant chr3-9928347-A-G is described in ClinVar as [Benign]. Clinvar id is 1164863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.920A>G	p.Gln307Arg	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.920A>G	p.Gln307Arg	missense_variant	11/19	1	NM_153460.4	ENSP00000384969.3		Q8NAC3-2
ENSG00000288550	ENST00000683484.1 linkuse as main transcript	n.836A>G		non_coding_transcript_exon_variant	10/24			ENSP00000507040.1		A0A804HIF2

Frequencies

GnomAD3 genomes

AF:

0.996

AC:

151585

AN:

152242

Hom.:

75465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.994

GnomAD3 exomes

AF:

0.995

AC:

245455

AN:

246602

Hom.:

122161

AF XY:

0.995

AC XY:

132916

AN XY:

133562

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.993

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.994

AC:

1443034

AN:

1451480

Hom.:

717326

Cov.:

AF XY:

0.994

AC XY:

716275

AN XY:

720402

show subpopulations

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.993

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.996

AC:

151703

AN:

152360

Hom.:

75524

Cov.:

AF XY:

0.996

AC XY:

74196

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

0.993

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.993

Gnomad4 OTH

AF:

0.994

Alfa

AF:

0.994

Hom.:

54799

Bravo

AF:

0.995

TwinsUK

AF:

0.996

AC:

3692

ALSPAC

AF:

0.994

AC:

3829

ESP6500AA

AF:

0.999

AC:

4401

ESP6500EA

AF:

0.994

AC:

8543

ExAC

AF:

0.996

AC:

120744

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.88

DANN

Benign

0.097

DEOGEN2

Benign

0.023

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.12

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

MetaRNN

Benign

6.7e-7

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.95

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

PrimateAI

Benign

0.27

PROVEAN

Benign

0.0

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

REVEL

Benign

0.010

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.047

MPC

0.25

ClinPred

0.0021

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.31

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