dbSNP rs5744292: IL18:n.1541A>G (chr11-112143413-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 ENST00000525547.5(IL18):n.1541A>G 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 0.186 in 490,862 control chromosomes in the GnomAD database, including 10,484 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 ( 2706 hom., cov: 34)

Exomes 𝑓: 0.20 ( 7778 hom. )

Consequence

IL18
ENST00000525547.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214

Publications

30 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=-0.9).

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.*183A>G		3_prime_UTR_variant	Exon 6 of 6	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.*183A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-27006T>C		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24733

AN:

152130

Hom.:

2705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.0867

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.197

AC:

66750

AN:

338614

Hom.:

7778

Cov.:

AF XY:

0.191

AC XY:

34049

AN XY:

178028

show subpopulations

African (AFR)

AF:

0.0392

AC:

385

AN:

9820

American (AMR)

AF:

0.135

AC:

1549

AN:

11466

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

1386

AN:

10688

East Asian (EAS)

AF:

0.00613

AC:

143

AN:

23334

South Asian (SAS)

AF:

0.0954

AC:

3271

AN:

34286

European-Finnish (FIN)

AF:

0.243

AC:

4990

AN:

20560

Middle Eastern (MID)

AF:

0.111

AC:

166

AN:

1490

European-Non Finnish (NFE)

AF:

0.247

AC:

51068

AN:

207046

Other (OTH)

AF:

0.190

AC:

3792

AN:

19924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2400

4799

7199

9598

11998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

24732

AN:

152248

Hom.:

2706

Cov.:

AF XY:

0.158

AC XY:

11786

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0454

AC:

1886

AN:

41566

American (AMR)

AF:

0.136

AC:

2084

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

431

AN:

3468

East Asian (EAS)

AF:

0.00540

AC:

AN:

5182

South Asian (SAS)

AF:

0.0872

AC:

421

AN:

4828

European-Finnish (FIN)

AF:

0.235

AC:

2486

AN:

10594

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16719

AN:

68012

Other (OTH)

AF:

0.155

AC:

328

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

990

1979

2969

3958

4948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.203

Hom.:

461

Bravo

AF:

0.153

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.67

PhyloP100

0.21

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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