11-112155162-T-A

Variant names:

• chr11-112155162-T-A
• rs12721559
• NM_001562.4:c.-8-101A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001562.4(IL18):​c.-8-101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4	c.-8-101A>T		intron_variant	Intron 1 of 5	ENST00000280357.12	NP_001553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.-8-101A>T		intron_variant	Intron 1 of 5	1	NM_001562.4	ENSP00000280357.7
ENSG00000255292	ENST00000532699.1	n.315-15257T>A		intron_variant	Intron 3 of 5	3		ENSP00000456434.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 443708 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 234088

African (AFR) AF: 0.00 AC: 0 AN: 13432

American (AMR) AF: 0.00 AC: 0 AN: 20078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13860

East Asian (EAS) AF: 0.00 AC: 0 AN: 31666

South Asian (SAS) AF: 0.00 AC: 0 AN: 35878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 263052

Other (OTH) AF: 0.00 AC: 0 AN: 24810

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.80
PhyloP100		-0.0010

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: rs12721559; hg19: chr11-112025885;