chr11-112155162-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001562.4(IL18):​c.-8-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 596,002 control chromosomes in the GnomAD database, including 58 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 0.0043 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (50 hom.)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4	c.-8-101A>G		intron_variant	Intron 1 of 5	ENST00000280357.12	NP_001553.1
IL18	NM_001386420.1	c.-29-80A>G		intron_variant	Intron 1 of 5		NP_001373349.1
IL18	NM_001243211.2	c.-8-101A>G		intron_variant	Intron 1 of 4		NP_001230140.1
IL18	XM_011542805.2	c.-29-80A>G		intron_variant	Intron 1 of 4		XP_011541107.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00430 AC: 654 AN: 152214 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00587 AC: 2606 AN: 443670 Hom.: 50 AF XY: 0.00548 AC XY: 1282 AN XY: 234072

Gnomad4 AFR exome AF: 0.0000744

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00512

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.0456

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.00429 AC: 653 AN: 152332 Hom.: 8 Cov.: 32 AF XY: 0.00609 AC XY: 454 AN XY: 74500

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.0426

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00365 Hom.: 0

Bravo AF: 0.00109

Asia WGS AF: 0.0100 AC: 36 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.81

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: rs12721559; hg19: chr11-112025885;