rs4937100

Variant names:

• chr11-112143063-A-G
• rs4937100
• ENST00000532699.1:n.315-27356A>G

Variant summary

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

The ENST00000532699.1(ENSG00000255292):​n.315-27356A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,776 control chromosomes in the GnomAD database, including 11,028 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 0.38 (11028 hom., cov: 33)
• Consequence: ENSG00000255292 ENST00000532699.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 6 publications found

Genes affected

ENSG00000255292 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4	c.*533T>C		downstream_gene_variant		ENST00000280357.12	NP_001553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000255292	ENST00000532699.1	n.315-27356A>G		intron_variant	Intron 3 of 5	3		ENSP00000456434.1
IL18	ENST00000280357.12	c.*533T>C		downstream_gene_variant		1	NM_001562.4	ENSP00000280357.7

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57007 AN: 151660 Hom.: 11002 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.376 AC: 57072 AN: 151776 Hom.: 11028 Cov.: 33 AF XY: 0.379 AC XY: 28081 AN XY: 74190

African (AFR) AF: 0.436 AC: 18060 AN: 41406

American (AMR) AF: 0.379 AC: 5783 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1305 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2466 AN: 5166

South Asian (SAS) AF: 0.586 AC: 2826 AN: 4822

European-Finnish (FIN) AF: 0.282 AC: 2948 AN: 10442

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.331 AC: 22461 AN: 67910

Other (OTH) AF: 0.403 AC: 849 AN: 2106

Alfa AF: 0.364 Hom.: 2904

Bravo AF: 0.380

Asia WGS AF: 0.547 AC: 1863 AN: 3408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		0.043

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: rs4937100; hg19: chr11-112013786;