Variant 3-9906418-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153480.2(IL17RE):c.323C>T(p.Thr108Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL17RE
NM_153480.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

Variant links:

Genes affected

IL17RE (HGNC:18439): (interleukin 17 receptor E) This gene encodes a transmembrane protein that functions as the receptor for interleukin-17C. The encoded protein signals to downstream components of the mitogen activated protein kinase (MAPK) pathway. Activity of this protein is important in the immune response to bacterial pathogens. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2013]

IL17RE links:

IL17RE (HGNC:):

IL17RE links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06204161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RE	NM_153480.2 linkuse as main transcript	c.323C>T	p.Thr108Ile	missense_variant	4/16	ENST00000383814.8	NP_705613.1	Q8NFR9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RE	ENST00000383814.8 linkuse as main transcript	c.323C>T	p.Thr108Ile	missense_variant	4/16	1	NM_153480.2	ENSP00000373325.3		Q8NFR9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.443C>T (p.T148I) alteration is located in exon 5 (coding exon 5) of the IL17RE gene. This alteration results from a C to T substitution at nucleotide position 443, causing the threonine (T) at amino acid position 148 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.94

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;N;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.29

N;N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.025

D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

0.029, 0.050

.;B;B;.

Vest4

0.20

MutPred

0.22

.;Loss of glycosylation at T108 (P = 0.0342);Loss of glycosylation at T108 (P = 0.0342);.;

MVP

0.061

ClinPred

0.058

GERP RS

-3.1

Varity_R

0.040

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over