Variant 13-20721910-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001385224.1(IL17D):c.565G>A(p.Ala189Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,606,522 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0860

Variant links:

Genes affected

IL17D (HGNC:5984): (interleukin 17D) The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent. [provided by RefSeq, Jul 2008]

IL17D 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=0.0061815083).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17D	NM_001385224.1 linkuse as main transcript	c.565G>A	p.Ala189Thr	missense_variant	2/2	ENST00000682841.1	NP_001372153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17D	ENST00000682841.1 linkuse as main transcript	c.565G>A	p.Ala189Thr	missense_variant	2/2		NM_001385224.1	ENSP00000508385	P1
IL17D	ENST00000304920.3 linkuse as main transcript	c.565G>A	p.Ala189Thr	missense_variant	3/3	1		ENSP00000302924	P1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00105

AC:

246

AN:

233394

Hom.:

AF XY:

0.000886

AC XY:

114

AN XY:

128712

show subpopulations

Gnomad AFR exome

AF:

0.000411

Gnomad AMR exome

AF:

0.0000877

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000824

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.00169

AC:

2458

AN:

1454230

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1142

AN XY:

723456

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000926

Gnomad4 NFE exome

AF:

0.00208

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152292

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000699

AC:

ESP6500EA

AF:

0.00214

AC:

ExAC

AF:

0.00123

AC:

148

EpiCase

AF:

0.00174

EpiControl

AF:

0.00148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.565G>A (p.A189T) alteration is located in exon 3 (coding exon 2) of the IL17D gene. This alteration results from a G to A substitution at nucleotide position 565, causing the alanine (A) at amino acid position 189 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.9

DANN

Benign

0.96

DEOGEN2

Benign

0.018

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.44

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.58

REVEL

Benign

0.018

Sift

Benign

0.35

Sift4G

Benign

0.42

Polyphen

0.066

Vest4

0.044

MVP

0.15

MPC

0.56

ClinPred

0.0029

GERP RS

-1.7

Varity_R

0.035

gMVP

0.36

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