dbSNP rs5744292: IL18:c.*183A>G (chr11-112143413-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001562.4(IL18):c.*183A>G variant causes a 3 prime UTR 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
NM_001562.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214

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 made for transcript

Verdict is Benign. Variant got -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	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
IL18	NM_001386420.1 link	c.*183A>G	3_prime_UTR_variant	Exon 6 of 6		NP_001373349.1
IL18	NM_001243211.2 link	c.*183A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001230140.1	Q14116-2A0A024R3E0
IL18	XM_011542805.2 link	c.*183A>G	3_prime_UTR_variant	Exon 5 of 5		XP_011541107.1	Q14116-2A0A024R3E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357 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

Gnomad4 AFR exome

AF:

0.0392

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.00613

Gnomad4 SAS exome

AF:

0.0954

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.162

AC:

24732

AN:

152248

Hom.:

2706

Cov.:

AF XY:

0.158

AC XY:

11786

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.0872

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.155

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

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over