11-112143366-T-C

Variant names:

• chr11-112143366-T-C
• rs360727
• NM_001562.4:c.*230A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001562.4(IL18):​c.*230A>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 0.969 in 369,870 control chromosomes in the GnomAD database, including 173,790 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 0.96 (70112 hom., cov: 34)
  • Exomes 𝑓: 0.98 (103678 hom.)
• Consequence: IL18 NM_001562.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 9 publications found

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]

ENSG00000255292 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	NM_001562.4	MANE Select	c.*230A>G		3_prime_UTR	Exon 6 of 6	NP_001553.1	Q14116-1
	IL18	NM_001386420.1		c.*230A>G		3_prime_UTR	Exon 6 of 6	NP_001373349.1	Q14116-1
	IL18	NM_001243211.2		c.*230A>G		3_prime_UTR	Exon 5 of 5	NP_001230140.1	Q14116-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	ENST00000280357.12	TSL:1 MANE Select	c.*230A>G		3_prime_UTR	Exon 6 of 6	ENSP00000280357.7	Q14116-1
	IL18	ENST00000524595.6	TSL:1	c.*230A>G		3_prime_UTR	Exon 5 of 5	ENSP00000434561.1	Q14116-2
	IL18	ENST00000525547.5	TSL:1	n.1588A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145937 AN: 152170 Hom.: 70070 Cov.: 34

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.959

GnomAD4 exome AF: 0.976 AC: 212344 AN: 217582 Hom.: 103678 Cov.: 2 AF XY: 0.975 AC XY: 109913 AN XY: 112758

African (AFR) AF: 0.905 AC: 6058 AN: 6694

American (AMR) AF: 0.977 AC: 7264 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 6914 AN: 7354

East Asian (EAS) AF: 1.00 AC: 15106 AN: 15110

South Asian (SAS) AF: 0.948 AC: 16374 AN: 17280

European-Finnish (FIN) AF: 0.984 AC: 12289 AN: 12494

Middle Eastern (MID) AF: 0.930 AC: 971 AN: 1044

European-Non Finnish (NFE) AF: 0.982 AC: 134044 AN: 136468

Other (OTH) AF: 0.972 AC: 13324 AN: 13706

GnomAD4 genome AF: 0.959 AC: 146038 AN: 152288 Hom.: 70112 Cov.: 34 AF XY: 0.960 AC XY: 71483 AN XY: 74460

African (AFR) AF: 0.906 AC: 37640 AN: 41532

American (AMR) AF: 0.972 AC: 14870 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 0.954 AC: 4608 AN: 4828

European-Finnish (FIN) AF: 0.982 AC: 10419 AN: 10614

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.982 AC: 66839 AN: 68040

Other (OTH) AF: 0.960 AC: 2027 AN: 2112

Alfa AF: 0.966 Hom.: 9180

Bravo AF: 0.957

Asia WGS AF: 0.971 AC: 3377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.15
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs360727;

hg19: chr11-112014089;