11-112144038-G-T

Variant names:

• chr11-112144038-G-T
• rs3882891
• NM_001562.4:c.361-221C>A

Variant summary

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

The NM_001562.4(IL18):​c.361-221C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,904 control chromosomes in the GnomAD database, including 22,233 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 0.54 (22233 hom., cov: 31)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	NM_001562.4	MANE Select	c.361-221C>A		intron	N/A	NP_001553.1
	IL18	NM_001386420.1		c.361-221C>A		intron	N/A	NP_001373349.1
	IL18	NM_001243211.2		c.349-221C>A		intron	N/A	NP_001230140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	ENST00000280357.12	TSL:1 MANE Select	c.361-221C>A		intron	N/A	ENSP00000280357.7
	IL18	ENST00000524595.6	TSL:1	c.349-221C>A		intron	N/A	ENSP00000434561.1
	IL18	ENST00000525547.5	TSL:1	n.1137-221C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81727 AN: 151784 Hom.: 22207 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81792 AN: 151904 Hom.: 22233 Cov.: 31 AF XY: 0.537 AC XY: 39866 AN XY: 74232

African (AFR) AF: 0.481 AC: 19924 AN: 41410

American (AMR) AF: 0.515 AC: 7859 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2494 AN: 5154

South Asian (SAS) AF: 0.673 AC: 3238 AN: 4814

European-Finnish (FIN) AF: 0.517 AC: 5441 AN: 10516

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39197 AN: 67968

Other (OTH) AF: 0.557 AC: 1177 AN: 2114

Alfa AF: 0.551 Hom.: 4443

Bravo AF: 0.532

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.62
PhyloP100		0.26
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

Other links and lift over

dbSNP: rs3882891; hg19: chr11-112014761;