rs75324888

chr3-9917726-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153460.4(IL17RC):c.119G>A(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,613,660 control chromosomes in the GnomAD database, including 678 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.036 (331 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (347 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.966

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011171997).
• BP6: Variant 3-9917726-G-A is Benign according to our data. Variant chr3-9917726-G-A is described in ClinVar as [Benign]. Clinvar id is 475928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4	c.119G>A	p.Arg40His	missense_variant	2/19	ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8	c.119G>A	p.Arg40His	missense_variant	2/19	1	NM_153460.4	P4

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5534 AN: 152098 Hom.: 328 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0359

GnomAD3 exomes AF: 0.0102 AC: 2520 AN: 246690 Hom.: 144 AF XY: 0.00777 AC XY: 1039 AN XY: 133686

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.00502

Gnomad ASJ exome AF: 0.00888

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000446

Gnomad OTH exome AF: 0.00580

GnomAD4 exome AF: 0.00399 AC: 5832 AN: 1461444 Hom.: 347 Cov.: 34 AF XY: 0.00350 AC XY: 2541 AN XY: 726984

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00604

Gnomad4 ASJ exome AF: 0.00945

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00947

GnomAD4 genome AF: 0.0364 AC: 5547 AN: 152216 Hom.: 331 Cov.: 32 AF XY: 0.0352 AC XY: 2617 AN XY: 74416

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.00737 Hom.: 103

Bravo AF: 0.0419

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.122 AC: 536

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0124 AC: 1509

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

IL17RC-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 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). -

Candidiasis, familial, 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	19
Dann	Benign	0.78
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.12	T;.;T;T;T;T;T;T;T
MetaRNN	Benign	0.0011	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.37	T
Sift4G	Benign	1.0	T;T;T;T;.;T;T;T;T
Polyphen		0.0, 0.0010	.;B;.;B;B;.;B;.;.
Vest4		0.24
MPC		0.29
ClinPred		0.0022	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.067
gMVP		0.20

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

Other links and lift over

dbSNP: rs75324888; hg19: chr3-9959410;