Genetic Variant ENST00000534225.1: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000534225.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18	NM_001562.4	MANE Select	c.-105C>T	5_prime_UTR	Exon 1 of 6	NP_001553.1
IL18	NM_001386420.1		c.-126C>T	5_prime_UTR	Exon 1 of 6	NP_001373349.1
IL18	NM_001243211.2		c.-105C>T	5_prime_UTR	Exon 1 of 5	NP_001230140.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18	ENST00000534225.1	TSL:1	n.92C>T	non_coding_transcript_exon	Exon 1 of 3
IL18	ENST00000280357.12	TSL:1 MANE Select	c.-105C>T	5_prime_UTR	Exon 1 of 6	ENSP00000280357.7
IL18	ENST00000524595.6	TSL:1	c.-105C>T	5_prime_UTR	Exon 1 of 5	ENSP00000434561.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over