rs455863

Positions:

• chr3-9914595-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153480.2(IL17RE):​c.1344G>A​(p.Pro448=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,613,342 control chromosomes in the GnomAD database, including 213,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18300 hom., cov: 32)
  • Exomes 𝑓: 0.51 (195284 hom.)
• Consequence: IL17RE NM_153480.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.691617E-6).
• BP7: Synonymous conserved (PhyloP=-4.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RE	NM_153480.2	c.1344G>A	p.Pro448=	synonymous_variant	14/16	ENST00000383814.8	NP_705613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RE	ENST00000383814.8	c.1344G>A	p.Pro448=	synonymous_variant	14/16	1	NM_153480.2	ENSP00000373325	P2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73002 AN: 151926 Hom.: 18287 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.483

GnomAD3 exomes AF: 0.460 AC: 115517 AN: 251132 Hom.: 28939 AF XY: 0.462 AC XY: 62719 AN XY: 135738

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.459

Gnomad EAS exome AF: 0.0811

Gnomad SAS exome AF: 0.349

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.508 AC: 742812 AN: 1461300 Hom.: 195284 Cov.: 41 AF XY: 0.505 AC XY: 367161 AN XY: 726962

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.0818

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.480 AC: 73047 AN: 152042 Hom.: 18300 Cov.: 32 AF XY: 0.478 AC XY: 35502 AN XY: 74322

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.488

Alfa AF: 0.522 Hom.: 45094

Bravo AF: 0.470

TwinsUK AF: 0.538 AC: 1995

ALSPAC AF: 0.525 AC: 2022

ESP6500AA AF: 0.415 AC: 1829

ESP6500EA AF: 0.532 AC: 4579

ExAC AF: 0.461 AC: 55926

Asia WGS AF: 0.288 AC: 996 AN: 3478

EpiCase AF: 0.538

EpiControl AF: 0.540

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.022
DANN	Benign	0.81
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0000057	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	0.66	N
REVEL	Benign	0.064
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);
ClinPred		0.020	T
GERP RS		-9.9

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: rs455863; hg19: chr3-9956279; COSMIC: COSV55970948; COSMIC: COSV55970948;