Genetic Variant NM_001385224.1:c.148G>A (chr13-20704149-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385224.1(IL17D):c.148G>A(p.Val50Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000059 in 1,354,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.683

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19375089).

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.148G>A	p.Val50Met	missense	Exon 1 of 2	NP_001372153.1	Q8TAD2
IL17D	NM_001385221.1		c.169G>A	p.Val57Met	missense	Exon 2 of 3	NP_001372150.1
IL17D	NM_001385222.1		c.169G>A	p.Val57Met	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.148G>A	p.Val50Met	missense	Exon 1 of 2	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3	TSL:1	c.148G>A	p.Val50Met	missense	Exon 2 of 3	ENSP00000302924.3	Q8TAD2
IL17D	ENST00000962835.1		c.148G>A	p.Val50Met	missense	Exon 2 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000743

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

71704

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000742

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:

0.00000414

AC:

AN:

1207898

Hom.:

Cov.:

AF XY:

0.00000504

AC XY:

AN XY:

594998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24420

American (AMR)

AF:

0.0000447

AC:

AN:

22366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19480

East Asian (EAS)

AF:

0.00

AC:

AN:

23312

South Asian (SAS)

AF:

0.00

AC:

AN:

61428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3266

European-Non Finnish (NFE)

AF:

0.00000307

AC:

AN:

977972

Other (OTH)

AF:

0.0000212

AC:

AN:

47224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000204

AC:

AN:

146998

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71676

show subpopulations

African (AFR)

AF:

0.0000741

AC:

AN:

40480

American (AMR)

AF:

0.00

AC:

AN:

14874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

4892

South Asian (SAS)

AF:

0.00

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66410

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.00

Hom.:

Bravo

AF:

0.0000189

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

Benign

0.31

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.022

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.79

M_CAP

Benign

0.062

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

0.68

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.14

REVEL

Benign

0.15

Sift

Benign

0.34

Sift4G

Benign

0.37

Polyphen

0.49

Vest4

0.095

MutPred

0.84

Gain of disorder (P = 0.0878)

MVP

0.30

MPC

0.67

ClinPred

0.069

GERP RS

0.55

PromoterAI

0.18

Neutral

(source)

Varity_R

0.075

gMVP

0.43

Mutation Taster

=86/14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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