rs145221454

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_017563.5(IL17RD):​c.1403C>T​(p.Ser468Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

IL17RD
NM_017563.5 missense

Scores

3
16

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.77
Variant links:
Genes affected
IL17RD (HGNC:17616): (interleukin 17 receptor D) This gene encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family. The encoded protein is a component of the interleukin-17 receptor signaling complex, and the interaction between this protein and IL-17R does not require the interleukin. The gene product also affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling. Alternate splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5
Variant 3-57098300-G-A is Pathogenic according to our data. Variant chr3-57098300-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 50870.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.112774014). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAd4 at 5 AD,Digenic gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL17RDNM_017563.5 linkuse as main transcriptc.1403C>T p.Ser468Leu missense_variant 12/13 ENST00000296318.12 NP_060033.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL17RDENST00000296318.12 linkuse as main transcriptc.1403C>T p.Ser468Leu missense_variant 12/131 NM_017563.5 ENSP00000296318 P1Q8NFM7-1
IL17RDENST00000320057.9 linkuse as main transcriptc.971C>T p.Ser324Leu missense_variant 13/141 ENSP00000322250 Q8NFM7-2
IL17RDENST00000463523.5 linkuse as main transcriptc.971C>T p.Ser324Leu missense_variant 12/131 ENSP00000417516 Q8NFM7-2
IL17RDENST00000469841.5 linkuse as main transcriptn.1340C>T non_coding_transcript_exon_variant 12/122

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251136
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000410
AC:
60
AN:
1461692
Hom.:
0
Cov.:
34
AF XY:
0.0000385
AC XY:
28
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000495
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000383
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hypogonadotropic hypogonadism 18 with anosmia Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 02, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.;.;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.30
N
LIST_S2
Uncertain
0.87
D;.;.;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.2
N;N;N;.
REVEL
Benign
0.13
Sift
Benign
0.15
T;T;T;.
Sift4G
Uncertain
0.024
D;D;D;.
Polyphen
0.60
P;.;.;.
Vest4
0.35
MVP
0.28
MPC
0.50
ClinPred
0.23
T
GERP RS
5.0
Varity_R
0.062
gMVP
0.26

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.

Other links and lift over

dbSNP: rs145221454; hg19: chr3-57132328; COSMIC: COSV56338034; API