3-9914595-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153480.2(IL17RE):​c.1344G>A​(p.Pro448Pro) 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
• Publications: 32 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	NM_153480.2	MANE Select	c.1344G>A	p.Pro448Pro	synonymous	Exon 14 of 16	NP_705613.1
	IL17RE	NM_001193380.2		c.1417G>A	p.Gly473Arg	missense	Exon 14 of 16	NP_001180309.1
	IL17RE	NM_153483.2		c.1464G>A	p.Pro488Pro	synonymous	Exon 15 of 17	NP_705616.2

Ensembl Transcripts

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

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

GnomAD2 exomes AF: 0.460 AC: 115517 AN: 251132 AF XY: 0.462

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 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

African (AFR) AF: 0.404 AC: 13528 AN: 33478

American (AMR) AF: 0.437 AC: 19553 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 11964 AN: 26102

East Asian (EAS) AF: 0.0818 AC: 3249 AN: 39698

South Asian (SAS) AF: 0.354 AC: 30510 AN: 86244

European-Finnish (FIN) AF: 0.579 AC: 30893 AN: 53396

Middle Eastern (MID) AF: 0.530 AC: 3054 AN: 5758

European-Non Finnish (NFE) AF: 0.540 AC: 600378 AN: 1111566

Other (OTH) AF: 0.492 AC: 29683 AN: 60364

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

African (AFR) AF: 0.412 AC: 17094 AN: 41458

American (AMR) AF: 0.485 AC: 7406 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3470

East Asian (EAS) AF: 0.0864 AC: 447 AN: 5176

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4822

European-Finnish (FIN) AF: 0.588 AC: 6216 AN: 10574

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36932 AN: 67952

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.514 Hom.: 96406

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
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
PhyloP100		-4.3
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
Mutation Taster		=96/4	polymorphism (auto)

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; COSMIC: COSV55970948; COSMIC: COSV55970948;