Genetic Variant IL18:c.-8-132C>G (chr11-112155193-G-C) – 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.-8-132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 533,580 control chromosomes in the GnomAD database, including 22,095 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 0.28 ( 6017 hom., cov: 32)

Exomes 𝑓: 0.28 ( 16078 hom. )

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

31 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4 link	c.-8-132C>G		intron_variant	Intron 1 of 5	ENST00000280357.12	NP_001553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12 link	c.-8-132C>G		intron_variant	Intron 1 of 5	1	NM_001562.4	ENSP00000280357.7
ENSG00000255292	ENST00000532699.1 link	n.315-15226G>C		intron_variant	Intron 3 of 5	3		ENSP00000456434.1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41913

AN:

151878

Hom.:

6019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.284

AC:

108198

AN:

381584

Hom.:

16078

AF XY:

0.282

AC XY:

56102

AN XY:

198726

show subpopulations

African (AFR)

AF:

0.213

AC:

2479

AN:

11624

American (AMR)

AF:

0.334

AC:

5341

AN:

16010

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

3464

AN:

12114

East Asian (EAS)

AF:

0.124

AC:

3727

AN:

29972

South Asian (SAS)

AF:

0.241

AC:

6734

AN:

27958

European-Finnish (FIN)

AF:

0.311

AC:

9678

AN:

31094

Middle Eastern (MID)

AF:

0.242

AC:

567

AN:

2342

European-Non Finnish (NFE)

AF:

0.306

AC:

69746

AN:

227702

Other (OTH)

AF:

0.284

AC:

6462

AN:

22768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3643

7286

10929

14572

18215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.276

AC:

41903

AN:

151996

Hom.:

6017

Cov.:

AF XY:

0.275

AC XY:

20450

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.217

AC:

9014

AN:

41464

American (AMR)

AF:

0.322

AC:

4919

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1018

AN:

3468

East Asian (EAS)

AF:

0.127

AC:

659

AN:

5170

South Asian (SAS)

AF:

0.229

AC:

1106

AN:

4824

European-Finnish (FIN)

AF:

0.313

AC:

3287

AN:

10516

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21034

AN:

67974

Other (OTH)

AF:

0.269

AC:

567

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1520

3040

4559

6079

7599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.166

Hom.:

339

Bravo

AF:

0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.6

(source)

DANN

Benign

0.61

PhyloP100

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over