rs7106524

Positions:

• chr11-112162913-G-A

Variant summary

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

The ENST00000280357.12(IL18):​c.-9+993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,042 control chromosomes in the GnomAD database, including 10,619 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 0.37 (10619 hom., cov: 32)
• Consequence: IL18 ENST00000280357.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18	NM_001562.4	c.-9+993C>T		intron_variant		ENST00000280357.12	NP_001553.1
IL18	NM_001243211.2	c.-9+993C>T		intron_variant			NP_001230140.1
IL18	NM_001386420.1	c.-30+993C>T		intron_variant			NP_001373349.1
IL18	XM_011542805.2	c.-30+993C>T		intron_variant			XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.-9+993C>T		intron_variant		1	NM_001562.4	ENSP00000280357	P3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56339 AN: 151924 Hom.: 10601 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.371 AC: 56390 AN: 152042 Hom.: 10619 Cov.: 32 AF XY: 0.373 AC XY: 27723 AN XY: 74302

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.393

Alfa AF: 0.361 Hom.: 1712

Bravo AF: 0.372

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7106524; hg19: chr11-112033636; COSMIC: COSV54781112; COSMIC: COSV54781112;