dbSNP rs1834481: IL18:c.91+488G>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 NM_001562.4(IL18):c.91+488G>C variant causes a intron 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
NM_001562.4 intron

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.

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.91+488G>C	intron	N/A	NP_001553.1	Q14116-1
IL18	NM_001386420.1		c.91+488G>C	intron	N/A	NP_001373349.1	Q14116-1
IL18	NM_001243211.2		c.79+1871G>C	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.91+488G>C	intron	N/A	ENSP00000280357.7	Q14116-1
IL18	ENST00000524595.6	TSL:1	c.79+1871G>C	intron	N/A	ENSP00000434561.1	Q14116-2
IL18	ENST00000534225.1	TSL:1	n.775G>C	non_coding_transcript_exon	Exon 3 of 3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over