Variant 3-9902952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.785

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
IL17RE	NM_153480.2 link	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 16	ENST00000383814.8	NP_705613.1	Q8NFR9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RE	ENST00000383814.8 link	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 16	1	NM_153480.2	ENSP00000373325.3		Q8NFR9-1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

927

AN:

152234

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00756

AC XY:

1027

AN XY:

135896

show subpopulations

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.:

Cov.:

AF XY:

0.00871

AC XY:

6334

AN XY:

727244

show subpopulations

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.:

Cov.:

AF XY:

0.00581

AC XY:

433

AN XY:

74504

show subpopulations

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.:

Bravo

AF:

0.00601

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00742

AC:

901

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

.;T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.69

T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;M;.

PrimateAI

Benign

0.30

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over