chr3-9928437-C-T

Position:

chr3-9928437-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000403601.8(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
ENST00000403601.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.794

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 Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
IL17RC	NM_153460.4 linkuse as main transcript	c.1010C>T	p.Pro337Leu	missense_variant	11/19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8 linkuse as main transcript	c.1010C>T	p.Pro337Leu	missense_variant	11/19	1	NM_153460.4	ENSP00000384969	P4	Q8NAC3-2

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4465

AN:

152208

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0344

AC XY:

24938

AN XY:

724034

show subpopulations

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.:

Cov.:

AF XY:

0.0280

AC XY:

2082

AN XY:

74482

show subpopulations

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.:

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:

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0364

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Candidiasis, familial, 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

0.078

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

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

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.37

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

MutationAssessor

Benign

1.3

.;.;.;L;.;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.0

.;D;D;D;.;D;D;D;D

REVEL

Benign

0.11

Sift

Benign

0.33

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

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

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

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