Genetic Variant NM_001385224.1:c.571C>T (chr13-20721916-C-T) – 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.571C>T(p.Leu191Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,630 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L191V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL17D
NM_001385224.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.702

Publications

2 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:

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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=0.1149576).

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.571C>T	p.Leu191Phe	missense	Exon 2 of 2	NP_001372153.1	Q8TAD2
IL17D	NM_001385221.1		c.592C>T	p.Leu198Phe	missense	Exon 3 of 3	NP_001372150.1
IL17D	NM_001385222.1		c.592C>T	p.Leu198Phe	missense	Exon 3 of 3	NP_001372151.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL17D	ENST00000682841.1	MANE Select	c.571C>T	p.Leu191Phe	missense	Exon 2 of 2	ENSP00000508385.1	Q8TAD2
IL17D	ENST00000304920.3	TSL:1	c.571C>T	p.Leu191Phe	missense	Exon 3 of 3	ENSP00000302924.3	Q8TAD2
IL17D	ENST00000962835.1		c.571C>T	p.Leu191Phe	missense	Exon 3 of 3	ENSP00000632894.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000431

AC:

AN:

232050

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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:

6.88e-7

AC:

AN:

1452630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.0000224

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110168

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.51

M_CAP

Benign

0.023

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

PhyloP100

0.70

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

REVEL

Benign

0.10

Sift

Benign

0.064

Sift4G

Benign

0.073

Polyphen

0.87

Vest4

0.19

MutPred

0.18

Gain of methylation at K190 (P = 0.0283)

MVP

0.25

MPC

0.92

ClinPred

0.22

GERP RS

3.8

Varity_R

0.14

gMVP

0.35

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over