dbSNP rs1834481: IL18:n.775G>C (chr11-112153104-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000534225.1(IL18):n.775G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 153,518 control chromosomes in the GnomAD database, including 2,731 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 ( 32 hom. )

Consequence

IL18
ENST00000534225.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.518

Publications

59 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=-0.88).

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.91+488G>C		intron_variant	Intron 3 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.91+488G>C		intron_variant	Intron 3 of 5	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-17315C>G		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24692

AN:

151926

Hom.:

2698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.00521

Gnomad SAS

AF:

0.0816

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.191

AC:

281

AN:

1474

Hom.:

Cov.:

AF XY:

0.189

AC XY:

146

AN XY:

772

show subpopulations

African (AFR)

AF:

0.0286

AC:

AN:

American (AMR)

AF:

0.0882

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0641

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AF:

0.261

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

231

AN:

1026

Other (OTH)

AF:

0.137

AC:

AN:

102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

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:

0.162

AC:

24691

AN:

152044

Hom.:

2699

Cov.:

AF XY:

0.158

AC XY:

11759

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0454

AC:

1883

AN:

41512

American (AMR)

AF:

0.136

AC:

2081

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3468

East Asian (EAS)

AF:

0.00503

AC:

AN:

5174

South Asian (SAS)

AF:

0.0821

AC:

395

AN:

4814

European-Finnish (FIN)

AF:

0.235

AC:

2481

AN:

10562

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16713

AN:

67934

Other (OTH)

AF:

0.155

AC:

328

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

970

1940

2909

3879

4849

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:

0.222

Hom.:

2307

Bravo

AF:

0.153

Asia WGS

AF:

0.0400

AC:

137

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.36

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

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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