rs2043055

chr11-112160901-A-Gchr11-112160901-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001562.4(IL18):c.-9+3005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,940 control chromosomes in the GnomAD database, including 12,346 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 0.40 (12346 hom., cov: 31)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18	NM_001562.4	c.-9+3005T>C		intron_variant		ENST00000280357.12
IL18	NM_001243211.2	c.-9+3005T>C		intron_variant
IL18	NM_001386420.1	c.-30+3005T>C		intron_variant
IL18	XM_011542805.2	c.-30+3005T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18	ENST00000280357.12	c.-9+3005T>C		intron_variant		1	NM_001562.4	P3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60585 AN: 151822 Hom.: 12317 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.399 AC: 60652 AN: 151940 Hom.: 12346 Cov.: 31 AF XY: 0.401 AC XY: 29759 AN XY: 74240

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.419

Alfa AF: 0.375 Hom.: 12978

Bravo AF: 0.403

Asia WGS AF: 0.555 AC: 1926 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.22
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs2043055; hg19: chr11-112031624;