NM_153480.2:c.172C>T

Variant names:

• chr3-9904055-C-T
• rs759166537
• NM_153480.2:c.172C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153480.2(IL17RE):​c.172C>T​(p.Arg58Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R58G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: IL17RE NM_153480.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.105
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052868485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153480.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	NM_153480.2	MANE Select	c.172C>T	p.Arg58Cys	missense	Exon 3 of 16	NP_705613.1	Q8NFR9-1
	IL17RE	NM_153483.2		c.292C>T	p.Arg98Cys	missense	Exon 4 of 17	NP_705616.2	Q8NFR9
	IL17RE	NM_001193380.2		c.172C>T	p.Arg58Cys	missense	Exon 3 of 16	NP_001180309.1	Q8NFR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	ENST00000383814.8	TSL:1 MANE Select	c.172C>T	p.Arg58Cys	missense	Exon 3 of 16	ENSP00000373325.3	Q8NFR9-1
	IL17RE	ENST00000421412.5	TSL:1	c.271C>T	p.Arg91Cys	missense	Exon 4 of 17	ENSP00000404916.1	J3KQN7
	IL17RE	ENST00000454190.6	TSL:2	c.172C>T	p.Arg58Cys	missense	Exon 3 of 16	ENSP00000388086.2	Q8NFR9-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000596 AC: 15 AN: 251490 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000439

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33 AN XY: 727224

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111988

Other (OTH) AF: 0.000149 AC: 9 AN: 60388

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000366 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.10
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.0080
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0030	B
Vest4		0.12
MVP		0.067
ClinPred		0.20	T
GERP RS		-0.32
Varity_R		0.079
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs759166537; hg19: chr3-9945739; COSMIC: COSV106094461; COSMIC: COSV106094461;