11-112164265-C-G

Variant names:

• chr11-112164265-C-G
• rs187238
• ENST00000532699.1:n.315-6154C>G

Variant summary

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

The ENST00000532699.1(ENSG00000255292):​n.315-6154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,136 control chromosomes in the GnomAD database, including 5,025 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 (5024 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: ENSG00000255292 ENST00000532699.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22
• Publications: 515 publications found

Genes affected

ENSG00000255292 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• 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: ENST00000532699.1. 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.-368G>C		upstream_gene	N/A	NP_001553.1	Q14116-1
	IL18	NM_001386420.1		c.-389G>C		upstream_gene	N/A	NP_001373349.1	Q14116-1
	IL18	NM_001243211.2		c.-368G>C		upstream_gene	N/A	NP_001230140.1	Q14116-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000255292	ENST00000532699.1	TSL:3	n.315-6154C>G		intron	N/A	ENSP00000456434.1	H3BRW5
	ENSG00000255292	ENST00000525987.5	TSL:4	n.320-6154C>G		intron	N/A
	ENSG00000255292	ENST00000531744.5	TSL:2	n.315-6154C>G		intron	N/A	ENSP00000456957.1	H3BRW5

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38315 AN: 152002 Hom.: 5025 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.268

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: 0.250 AC: 4 AN: 16 Hom.: 1 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 3 AN: 14

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.252 AC: 38306 AN: 152120 Hom.: 5024 Cov.: 32 AF XY: 0.252 AC XY: 18737 AN XY: 74386

African (AFR) AF: 0.211 AC: 8750 AN: 41522

American (AMR) AF: 0.299 AC: 4566 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3470

East Asian (EAS) AF: 0.129 AC: 666 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4832

European-Finnish (FIN) AF: 0.287 AC: 3029 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18511 AN: 67962

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.141 Hom.: 263

Bravo AF: 0.253

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.51
DANN	Benign	0.75
PhyloP100		-4.2
PromoterAI		0.015	Neutral

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: rs187238;

hg19: chr11-112034988;