rs795467

Variant names:

• chr11-112160357-G-A
• rs795467
• NM_001562.4:c.-9+3549C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-112160357-G-A
• chr11-112160357-G-C
• chr11-112160357-G-T

Variant summary

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

The NM_001562.4(IL18):​c.-9+3549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 140,128 control chromosomes in the GnomAD database, including 5,035 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 0.27 (5035 hom., cov: 27)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4	c.-9+3549C>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.-9+3549C>T		intron_variant	Intron 1 of 5	1	NM_001562.4	ENSP00000280357.7
ENSG00000255292	ENST00000532699.1	n.315-10062G>A		intron_variant	Intron 3 of 5	3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 37811 AN: 140062 Hom.: 5036 Cov.: 27

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.270 AC: 37797 AN: 140128 Hom.: 5035 Cov.: 27 AF XY: 0.273 AC XY: 18339 AN XY: 67224

African (AFR) AF: 0.225 AC: 8392 AN: 37348

American (AMR) AF: 0.330 AC: 4505 AN: 13634

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 932 AN: 3400

East Asian (EAS) AF: 0.142 AC: 627 AN: 4418

South Asian (SAS) AF: 0.238 AC: 1008 AN: 4230

European-Finnish (FIN) AF: 0.346 AC: 2814 AN: 8130

Middle Eastern (MID) AF: 0.319 AC: 79 AN: 248

European-Non Finnish (NFE) AF: 0.284 AC: 18708 AN: 65920

Other (OTH) AF: 0.271 AC: 519 AN: 1918

Alfa AF: 0.245 Hom.: 2632

Bravo AF: 0.256

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs795467; hg19: chr11-112031080;