Genetic Variant IL18:c.-8-101A>G (chr11-112155162-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001562.4(IL18):c.-8-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 596,002 control chromosomes in the GnomAD database, including 58 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 0.0043 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 50 hom. )

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4 link	c.-8-101A>G		intron_variant	Intron 1 of 5	ENST00000280357.12	NP_001553.1	Q14116-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12 link	c.-8-101A>G		intron_variant	Intron 1 of 5	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-15257T>C		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.00430

AC:

654

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0426

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.00587

AC:

2606

AN:

443670

Hom.:

AF XY:

0.00548

AC XY:

1282

AN XY:

234072

show subpopulations

African (AFR)

AF:

0.0000744

AC:

AN:

13432

American (AMR)

AF:

0.00

AC:

AN:

20078

Ashkenazi Jewish (ASJ)

AF:

0.00512

AC:

AN:

13860

East Asian (EAS)

AF:

0.0107

AC:

340

AN:

31658

South Asian (SAS)

AF:

0.00301

AC:

108

AN:

35872

European-Finnish (FIN)

AF:

0.0456

AC:

1720

AN:

37746

Middle Eastern (MID)

AF:

0.000316

AC:

AN:

3168

European-Non Finnish (NFE)

AF:

0.00102

AC:

268

AN:

263048

Other (OTH)

AF:

0.00391

AC:

AN:

24808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

120

239

359

478

598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00429

AC:

653

AN:

152332

Hom.:

Cov.:

AF XY:

0.00609

AC XY:

454

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41582

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3468

East Asian (EAS)

AF:

0.0131

AC:

AN:

5188

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0426

AC:

452

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00147

AC:

100

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00365

Hom.:

Bravo

AF:

0.00109

Asia WGS

AF:

0.0100

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.1

(source)

DANN

Benign

0.81

PhyloP100

-0.0010

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over