3-9902952-C-T

Position:

• chr3-9902952-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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]

IL17RE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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. gnomad4_exome 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 gnomad4_exome. There are 6334 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RE	NM_153480.2	c.20C>T	p.Ala7Val	missense_variant	1/16	ENST00000383814.8	NP_705613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RE	ENST00000383814.8	c.20C>T	p.Ala7Val	missense_variant	1/16	1	NM_153480.2	ENSP00000373325.3

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

GnomAD3 exomes AF: 0.00711 AC: 1788 AN: 251392 Hom.: 15 AF XY: 0.00756 AC XY: 1027 AN XY: 135896

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 SAS exome AF: 0.00869

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

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00481

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00846

Gnomad4 FIN exome AF: 0.00114

Gnomad4 NFE exome AF: 0.00958

Gnomad4 OTH exome AF: 0.00886

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

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00906

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00917 Hom.: 14

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

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;T;T;T
MetaRNN	Benign	0.0049	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;M;M;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.79	N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.025, 0.042	.;B;B;.
Vest4		0.25
MVP		0.10
ClinPred		0.034	T
GERP RS		2.3
Varity_R		0.051
gMVP		0.61

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: rs12492494; hg19: chr3-9944636; COSMIC: COSV55967294;