rs115419420

Positions:

• chr3-9928437-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153460.4(IL17RC):​c.1010C>T​(p.Pro337Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,607,348 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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. P337S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.029 (61 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1049 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008392245).
• BP6: Variant 3-9928437-C-T is Benign according to our data. Variant chr3-9928437-C-T is described in ClinVar as [Benign]. Clinvar id is 475919.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-9928437-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0293 (4465/152326) while in subpopulation NFE AF= 0.0385 (2621/68020). AF 95% confidence interval is 0.0373. There are 61 homozygotes in gnomad4. There are 2082 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4	c.1010C>T	p.Pro337Leu	missense_variant	11/19	ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8	c.1010C>T	p.Pro337Leu	missense_variant	11/19	1	NM_153460.4	P4

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4465 AN: 152208 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.0256 AC: 6242 AN: 243830 Hom.: 104 AF XY: 0.0250 AC XY: 3310 AN XY: 132634

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.0161

Gnomad ASJ exome AF: 0.0165

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00719

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.0377

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0354 AC: 51562 AN: 1455022 Hom.: 1049 Cov.: 41 AF XY: 0.0344 AC XY: 24938 AN XY: 724034

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00752

Gnomad4 FIN exome AF: 0.0302

Gnomad4 NFE exome AF: 0.0408

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0293 AC: 4465 AN: 152326 Hom.: 61 Cov.: 33 AF XY: 0.0280 AC XY: 2082 AN XY: 74482

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0385

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0323 Hom.: 30

Bravo AF: 0.0292

TwinsUK AF: 0.0343 AC: 127

ALSPAC AF: 0.0506 AC: 195

ESP6500AA AF: 0.0279 AC: 123

ESP6500EA AF: 0.0377 AC: 324

ExAC AF: 0.0256 AC: 3106

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0352

EpiControl AF: 0.0364

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Candidiasis, familial, 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.85	T;.;D;D;D;D;D;T;D
MetaRNN	Benign	0.0084	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Benign	0.34	T
REVEL	Benign	0.11
Sift4G	Benign	0.87	T;T;T;T;.;T;T;T;T
Polyphen		0.015, 0.80, 0.0090	.;B;.;P;B;.;B;.;.
Vest4		0.19
MPC		0.24
ClinPred		0.0086	T
GERP RS		2.7
Varity_R		0.22
gMVP		0.52

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: rs115419420; hg19: chr3-9970121;