3-9902952-C-T

Variant names:

• chr3-9902952-C-T
• rs12492494
• NM_153480.2:c.20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153480.2(IL17RE):​c.20C>T​(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,614,230 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (83 hom.)
• Consequence: IL17RE NM_153480.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.785
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004919827).
• BP6: Variant 3-9902952-C-T is Benign according to our data. Variant chr3-9902952-C-T is described in ClinVar as Benign. ClinVar VariationId is 773438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00869 (12705/1461878) while in subpopulation MID AF = 0.0224 (129/5768). AF 95% confidence interval is 0.0192. There are 83 homozygotes in GnomAdExome4. There are 6334 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.20C>T	p.Ala7Val	missense	Exon 1 of 16	NP_705613.1	Q8NFR9-1
	IL17RE	NM_153483.2		c.140C>T	p.Ala47Val	missense	Exon 2 of 17	NP_705616.2	Q8NFR9
	IL17RE	NM_001193380.2		c.20C>T	p.Ala7Val	missense	Exon 1 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.20C>T	p.Ala7Val	missense	Exon 1 of 16	ENSP00000373325.3	Q8NFR9-1
	IL17RE	ENST00000421412.5	TSL:1	c.119C>T	p.Ala40Val	missense	Exon 2 of 17	ENSP00000404916.1	J3KQN7
	IL17RE	ENST00000865435.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 13	ENSP00000535494.1

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 927 AN: 152234 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00906

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00711 AC: 1788 AN: 251392 AF XY: 0.00756

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00987

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.00869 AC: 12705 AN: 1461878 Hom.: 83 Cov.: 32 AF XY: 0.00871 AC XY: 6334 AN XY: 727244

African (AFR) AF: 0.00140 AC: 47 AN: 33480

American (AMR) AF: 0.00481 AC: 215 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 331 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00846 AC: 730 AN: 86256

European-Finnish (FIN) AF: 0.00114 AC: 61 AN: 53420

Middle Eastern (MID) AF: 0.0224 AC: 129 AN: 5768

European-Non Finnish (NFE) AF: 0.00958 AC: 10655 AN: 1112000

Other (OTH) AF: 0.00886 AC: 535 AN: 60396

GnomAD4 genome AF: 0.00608 AC: 927 AN: 152352 Hom.: 7 Cov.: 32 AF XY: 0.00581 AC XY: 433 AN XY: 74504

African (AFR) AF: 0.00178 AC: 74 AN: 41590

American (AMR) AF: 0.00817 AC: 125 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00906 AC: 616 AN: 68018

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00867 Hom.: 17

Bravo AF: 0.00601

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00884 AC: 76

ExAC AF: 0.00742 AC: 901

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.0113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.79
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.025	B
Vest4		0.25
MVP		0.10
ClinPred		0.034	T
GERP RS		2.3
PromoterAI		-0.079	Neutral
Varity_R		0.051
gMVP		0.61
Mutation Taster		=99/1	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: rs12492494; hg19: chr3-9944636; COSMIC: COSV55967294;