11-112150193-T-G

Variant names:

• chr11-112150193-T-G
• rs549908
• NM_001562.4:c.105A>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001562.4(IL18):​c.105A>C​(p.Ser35Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,552,018 control chromosomes in the GnomAD database, including 66,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5863 hom., cov: 32)
  • Exomes 𝑓: 0.29 (60349 hom.)
• Consequence: IL18 NM_001562.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0950
• Publications: 110 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-112150193-T-G is Benign according to our data. Variant chr11-112150193-T-G is described in ClinVar as Benign. ClinVar VariationId is 812621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	NM_001562.4	MANE Select	c.105A>C	p.Ser35Ser	synonymous	Exon 4 of 6	NP_001553.1
	IL18	NM_001386420.1		c.105A>C	p.Ser35Ser	synonymous	Exon 4 of 6	NP_001373349.1
	IL18	NM_001243211.2		c.93A>C	p.Ser31Ser	synonymous	Exon 3 of 5	NP_001230140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	ENST00000280357.12	TSL:1 MANE Select	c.105A>C	p.Ser35Ser	synonymous	Exon 4 of 6	ENSP00000280357.7
	IL18	ENST00000524595.6	TSL:1	c.93A>C	p.Ser31Ser	synonymous	Exon 3 of 5	ENSP00000434561.1
	IL18	ENST00000525547.5	TSL:1	n.881A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41208 AN: 152004 Hom.: 5865 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.270

GnomAD2 exomes AF: 0.285 AC: 68341 AN: 239770 AF XY: 0.285

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.290 AC: 406317 AN: 1399896 Hom.: 60349 Cov.: 26 AF XY: 0.290 AC XY: 202736 AN XY: 699340

African (AFR) AF: 0.187 AC: 5978 AN: 31984

American (AMR) AF: 0.331 AC: 13920 AN: 42002

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7239 AN: 25436

East Asian (EAS) AF: 0.128 AC: 5022 AN: 39388

South Asian (SAS) AF: 0.244 AC: 20239 AN: 82988

European-Finnish (FIN) AF: 0.310 AC: 16498 AN: 53164

Middle Eastern (MID) AF: 0.251 AC: 1393 AN: 5558

European-Non Finnish (NFE) AF: 0.301 AC: 319629 AN: 1061044

Other (OTH) AF: 0.281 AC: 16399 AN: 58332

GnomAD4 genome AF: 0.271 AC: 41192 AN: 152122 Hom.: 5863 Cov.: 32 AF XY: 0.271 AC XY: 20120 AN XY: 74362

African (AFR) AF: 0.201 AC: 8338 AN: 41526

American (AMR) AF: 0.321 AC: 4900 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3466

East Asian (EAS) AF: 0.128 AC: 666 AN: 5190

South Asian (SAS) AF: 0.230 AC: 1112 AN: 4826

European-Finnish (FIN) AF: 0.311 AC: 3281 AN: 10564

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21023 AN: 67958

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.296 Hom.: 10302

Bravo AF: 0.270

Asia WGS AF: 0.193 AC: 673 AN: 3474

EpiCase AF: 0.297

EpiControl AF: 0.300

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.3
DANN	Benign	0.88
PhyloP100		-0.095
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: rs549908; hg19: chr11-112020916; COSMIC: COSV54780703; COSMIC: COSV54780703;