dbSNP rs4988359: IL18:c.-8-131A>G (chr11-112155192-T-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.-8-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 540,982 control chromosomes in the GnomAD database, including 11,406 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 0.16 ( 2699 hom., cov: 32)

Exomes 𝑓: 0.19 ( 8707 hom. )

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

Publications

9 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4 link	c.-8-131A>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.-8-131A>G		intron_variant	Intron 1 of 5	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-15227T>C		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24721

AN:

152076

Hom.:

2698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.00538

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.192

AC:

74655

AN:

388788

Hom.:

8707

AF XY:

0.188

AC XY:

38112

AN XY:

202654

show subpopulations

African (AFR)

AF:

0.0416

AC:

491

AN:

11796

American (AMR)

AF:

0.130

AC:

2136

AN:

16424

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

1550

AN:

12288

East Asian (EAS)

AF:

0.00658

AC:

199

AN:

30226

South Asian (SAS)

AF:

0.0776

AC:

2276

AN:

29332

European-Finnish (FIN)

AF:

0.236

AC:

7573

AN:

32066

Middle Eastern (MID)

AF:

0.110

AC:

267

AN:

2418

European-Non Finnish (NFE)

AF:

0.242

AC:

55946

AN:

231218

Other (OTH)

AF:

0.183

AC:

4217

AN:

23020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2728

5457

8185

10914

13642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.162

AC:

24720

AN:

152194

Hom.:

2699

Cov.:

AF XY:

0.158

AC XY:

11771

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0453

AC:

1883

AN:

41566

American (AMR)

AF:

0.137

AC:

2093

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3468

East Asian (EAS)

AF:

0.00520

AC:

AN:

5188

South Asian (SAS)

AF:

0.0825

AC:

398

AN:

4826

European-Finnish (FIN)

AF:

0.234

AC:

2483

AN:

10592

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16724

AN:

67954

Other (OTH)

AF:

0.155

AC:

328

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

998

1997

2995

3994

4992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.213

Hom.:

1324

Bravo

AF:

0.153

Asia WGS

AF:

0.0390

AC:

136

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.2

(source)

DANN

Benign

0.80

PhyloP100

0.022

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