dbSNP rs360717: IL18:n.92C>T (chr11-112164002-G-A) – 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.92C>T 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 0.252 in 152,274 control chromosomes in the GnomAD database, including 5,022 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 0.25 ( 5019 hom., cov: 33)

Exomes 𝑓: 0.25 ( 3 hom. )

Consequence

IL18
ENST00000534225.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

52 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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4 link	c.-105C>T		5_prime_UTR_variant	Exon 1 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.-105C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-6417G>A		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38295

AN:

151962

Hom.:

5020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.247

AC:

AN:

194

Hom.:

Cov.:

AF XY:

0.220

AC XY:

AN XY:

118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.289

AC:

AN:

128

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.196

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.252

AC:

38286

AN:

152080

Hom.:

5019

Cov.:

AF XY:

0.252

AC XY:

18721

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.210

AC:

8728

AN:

41476

American (AMR)

AF:

0.299

AC:

4573

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

926

AN:

3468

East Asian (EAS)

AF:

0.128

AC:

663

AN:

5176

South Asian (SAS)

AF:

0.214

AC:

1030

AN:

4824

European-Finnish (FIN)

AF:

0.287

AC:

3031

AN:

10572

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18517

AN:

67970

Other (OTH)

AF:

0.248

AC:

521

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1476

2952

4428

5904

7380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.264

Hom.:

14732

Bravo

AF:

0.253

Asia WGS

AF:

0.185

AC:

646

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.65

PhyloP100

-1.4

PromoterAI

-0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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