Genetic Variant IL18:c.-8-3937T>A (chr11-112158998-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001562.4(IL18):c.-8-3937T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,260 control chromosomes in the GnomAD database, including 22,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 22414 hom., cov: 30)

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.520

Publications

12 publications found

Variant links:

Genes affected

IL18 (HGNC:5986): (interleukin 18) The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]

IL18 links:

ENSG00000255292 (HGNC:):

ENSG00000255292 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18	NM_001562.4	MANE Select	c.-8-3937T>A	intron	N/A	NP_001553.1	Q14116-1
IL18	NM_001386420.1		c.-29-3916T>A	intron	N/A	NP_001373349.1	Q14116-1
IL18	NM_001243211.2		c.-8-3937T>A	intron	N/A	NP_001230140.1	Q14116-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18	ENST00000280357.12	TSL:1 MANE Select	c.-8-3937T>A	intron	N/A	ENSP00000280357.7	Q14116-1
IL18	ENST00000524595.6	TSL:1	c.-8-3937T>A	intron	N/A	ENSP00000434561.1	Q14116-2
ENSG00000255292	ENST00000532699.1	TSL:3	n.315-11421A>T	intron	N/A	ENSP00000456434.1	H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82097

AN:

151142

Hom.:

22385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.543

AC:

82163

AN:

151260

Hom.:

22414

Cov.:

AF XY:

0.542

AC XY:

40014

AN XY:

73888

show subpopulations

African (AFR)

AF:

0.495

AC:

20333

AN:

41082

American (AMR)

AF:

0.520

AC:

7889

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1739

AN:

3468

East Asian (EAS)

AF:

0.483

AC:

2484

AN:

5140

South Asian (SAS)

AF:

0.676

AC:

3235

AN:

4788

European-Finnish (FIN)

AF:

0.518

AC:

5414

AN:

10448

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39165

AN:

67860

Other (OTH)

AF:

0.565

AC:

1181

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1886

3772

5659

7545

9431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.549

Hom.:

2763

Bravo

AF:

0.536

Asia WGS

AF:

0.590

AC:

2051

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over