chr3-57097757-G-A

Position:

chr3-57097757-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017563.5(IL17RD):c.1946C>T(p.Thr649Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,601,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

IL17RD
NM_017563.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0800

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]

IL17RD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031660467).

BS2

High AC in GnomAd4 at 23 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RD	NM_017563.5 linkuse as main transcript	c.1946C>T	p.Thr649Met	missense_variant	12/13	ENST00000296318.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RD	ENST00000296318.12 linkuse as main transcript	c.1946C>T	p.Thr649Met	missense_variant	12/13	1	NM_017563.5	P1	Q8NFM7-1
IL17RD	ENST00000320057.9 linkuse as main transcript	c.1514C>T	p.Thr505Met	missense_variant	13/14	1			Q8NFM7-2
IL17RD	ENST00000463523.5 linkuse as main transcript	c.1514C>T	p.Thr505Met	missense_variant	12/13	1			Q8NFM7-2
IL17RD	ENST00000469841.5 linkuse as main transcript	n.1883C>T		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000192

AC:

AN:

239098

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

129306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

265

AN:

1449508

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

127

AN XY:

719598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000151

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 649 of the IL17RD protein (p.Thr649Met). This variant is present in population databases (rs201420445, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with IL17RD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1432607). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IL17RD protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.9

DANN

Benign

0.97

DEOGEN2

Benign

0.067

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.67

T;.;.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.87

N;N;N;.

REVEL

Benign

0.043

Sift

Uncertain

0.0060

D;D;D;.

Sift4G

Uncertain

0.013

D;D;D;.

Polyphen

0.0010

B;.;.;.

Vest4

0.091

MVP

0.15

MPC

0.13

ClinPred

0.039

GERP RS

-2.6

Varity_R

0.021

gMVP

0.12

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