3-9914595-G-C

Variant names:

• chr3-9914595-G-C
• rs455863
• NM_153480.2:c.1344G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193380.2(IL17RE):​c.1417G>C​(p.Gly473Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IL17RE NM_001193380.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14104515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193380.2. 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.1344G>C	p.Pro448Pro	synonymous	Exon 14 of 16	NP_705613.1	Q8NFR9-1
	IL17RE	NM_001193380.2		c.1417G>C	p.Gly473Arg	missense	Exon 14 of 16	NP_001180309.1	Q8NFR9-3
	IL17RE	NM_153483.2		c.1464G>C	p.Pro488Pro	synonymous	Exon 15 of 17	NP_705616.2	Q8NFR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	ENST00000383814.8	TSL:1 MANE Select	c.1344G>C	p.Pro448Pro	synonymous	Exon 14 of 16	ENSP00000373325.3	Q8NFR9-1
	IL17RE	ENST00000421412.5	TSL:1	c.1443G>C	p.Pro481Pro	synonymous	Exon 15 of 17	ENSP00000404916.1	J3KQN7
	IL17RE	ENST00000454190.6	TSL:2	c.1417G>C	p.Gly473Arg	missense	Exon 14 of 16	ENSP00000388086.2	Q8NFR9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461648 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.016
DANN	Benign	0.70
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
PhyloP100		-4.3
PROVEAN	Benign	0.66	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.29		Gain of helix (P = 0.0425)
MVP		0.085
ClinPred		0.057	T
GERP RS		-9.9
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs455863; hg19: chr3-9956279;