dbSNP rs360718: IL18:n.78T>G (chr11-112164016-A-C) – 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.78T>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 0.256 in 152,320 control chromosomes in the GnomAD database, including 5,162 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 0.26 ( 5156 hom., cov: 33)

Exomes 𝑓: 0.29 ( 6 hom. )

Consequence

IL18
ENST00000534225.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.540

Publications

49 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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4 link	c.-119T>G		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.-119T>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_001562.4	ENSP00000280357.7		Q14116-1
ENSG00000255292	ENST00000532699.1 link	n.315-6403A>C		intron_variant	Intron 3 of 5	3		ENSP00000456434.1		H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38910

AN:

151982

Hom.:

5157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.286

AC:

AN:

220

Hom.:

Cov.:

AF XY:

0.282

AC XY:

AN XY:

142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.286

AC:

AN:

126

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.280

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

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:

0.256

AC:

38902

AN:

152100

Hom.:

5156

Cov.:

AF XY:

0.256

AC XY:

19013

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.225

AC:

9317

AN:

41478

American (AMR)

AF:

0.300

AC:

4584

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

926

AN:

3466

East Asian (EAS)

AF:

0.128

AC:

663

AN:

5166

South Asian (SAS)

AF:

0.214

AC:

1031

AN:

4826

European-Finnish (FIN)

AF:

0.286

AC:

3031

AN:

10580

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18525

AN:

67992

Other (OTH)

AF:

0.251

AC:

528

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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.:

2605

Bravo

AF:

0.257

Asia WGS

AF:

0.186

AC:

649

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.8

(source)

DANN

Benign

0.54

PhyloP100

0.54

PromoterAI

0.0091

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