Genetic Variant NM_001385224.1:c.77C>T (chr13-20704078-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.77C>T(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,118,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.483

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=0.1053409).

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.77C>T	p.Ala26Val	missense	Exon 1 of 2	NP_001372153.1	Q8TAD2
IL17D	NM_001385221.1		c.98C>T	p.Ala33Val	missense	Exon 2 of 3	NP_001372150.1
IL17D	NM_001385222.1		c.98C>T	p.Ala33Val	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.77C>T	p.Ala26Val	missense	Exon 1 of 2	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3	TSL:1	c.77C>T	p.Ala26Val	missense	Exon 2 of 3	ENSP00000302924.3	Q8TAD2
IL17D	ENST00000962835.1		c.77C>T	p.Ala26Val	missense	Exon 2 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

143324

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000507

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:

0.000385

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000149

AC:

AN:

6714

AF XY:

0.000217

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

264

AN:

974934

Hom.:

Cov.:

AF XY:

0.000284

AC XY:

132

AN XY:

464354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18764

American (AMR)

AF:

0.000206

AC:

AN:

4858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9380

East Asian (EAS)

AF:

0.00

AC:

AN:

14218

South Asian (SAS)

AF:

0.00

AC:

AN:

21100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2332

European-Non Finnish (NFE)

AF:

0.000285

AC:

244

AN:

855402

Other (OTH)

AF:

0.000538

AC:

AN:

35330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000188

AC:

AN:

143324

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

69880

show subpopulations

African (AFR)

AF:

0.0000507

AC:

AN:

39434

American (AMR)

AF:

0.00

AC:

AN:

14628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3364

East Asian (EAS)

AF:

0.00

AC:

AN:

4678

South Asian (SAS)

AF:

0.00

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000385

AC:

AN:

64992

Other (OTH)

AF:

0.00

AC:

AN:

1978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000356

Hom.:

Bravo

AF:

0.000159

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

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.43

M_CAP

Benign

0.047

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.48

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

REVEL

Benign

0.072

Sift

Benign

0.30

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.057

MutPred

0.48

Loss of relative solvent accessibility (P = 0.0186)

MVP

0.38

MPC

0.58

ClinPred

0.029

GERP RS

1.8

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.075

gMVP

0.36

Mutation Taster

=94/6

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