Genetic Variant IL17D:p.Pro85Leu (chr13-20704255-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001385224.1(IL17D):c.254C>T(p.Pro85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 1,303,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08915356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385224.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL17D	NM_001385224.1	MANE Select	c.254C>T	p.Pro85Leu	missense	Exon 1 of 2	NP_001372153.1	Q8TAD2
IL17D	NM_001385221.1		c.275C>T	p.Pro92Leu	missense	Exon 2 of 3	NP_001372150.1
IL17D	NM_001385222.1		c.275C>T	p.Pro92Leu	missense	Exon 2 of 3	NP_001372151.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL17D	ENST00000682841.1	MANE Select	c.254C>T	p.Pro85Leu	missense	Exon 1 of 2	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3	TSL:1	c.254C>T	p.Pro85Leu	missense	Exon 2 of 3	ENSP00000302924.3	Q8TAD2
IL17D	ENST00000962835.1		c.254C>T	p.Pro85Leu	missense	Exon 2 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes

AF:

0.000234

AC:

AN:

145434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000783

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000677

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000506

GnomAD2 exomes

AF:

0.0000586

AC:

AN:

17064

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1158280

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

564686

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

23062

American (AMR)

AF:

0.0000861

AC:

AN:

11614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15446

East Asian (EAS)

AF:

0.00

AC:

AN:

24808

South Asian (SAS)

AF:

0.00

AC:

AN:

45592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3080

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

962512

Other (OTH)

AF:

0.000109

AC:

AN:

45746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000240

AC:

AN:

145534

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

AN XY:

71016

show subpopulations

African (AFR)

AF:

0.000806

AC:

AN:

39704

American (AMR)

AF:

0.0000676

AC:

AN:

14798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.00

AC:

AN:

4608

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

9630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65384

Other (OTH)

AF:

0.000500

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000423

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.031

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

3.3

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.16

Sift

Benign

0.70

Sift4G

Uncertain

0.030

Polyphen

0.88

Vest4

0.27

MutPred

0.50

Loss of catalytic residue at P84 (P = 0.0131)

MVP

0.64

MPC

1.1

ClinPred

0.33

GERP RS

2.4

Varity_R

0.36

gMVP

0.52

Mutation Taster

=57/43

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over