ENST00000497194.6:c.-553A>G

Variant names:

• chr11-71999432-A-G
• rs2298455
• ENST00000497194.6:c.-553A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000497194.6(IL18BP):​c.-553A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL18BP ENST00000497194.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 17 publications found

Genes affected

IL18BP (HGNC:5987): (interleukin 18 binding protein) The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

IL18BP Gene-Disease associations (from GenCC):

• hepatitis, fulminant viral, susceptibility to

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000497194.6. 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
	IL18BP	NM_001039660.2	MANE Select	c.-59+413A>G		intron	N/A	NP_001034749.1
	IL18BP	NM_005699.3		c.-553A>G		5_prime_UTR	Exon 1 of 4	NP_005690.2
	IL18BP	NM_173042.2		c.-553A>G		5_prime_UTR	Exon 1 of 5	NP_766630.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18BP	ENST00000497194.6	TSL:1	c.-553A>G		5_prime_UTR	Exon 1 of 4	ENSP00000434717.1
	IL18BP	ENST00000404792.5	TSL:1	c.-553A>G		5_prime_UTR	Exon 1 of 5	ENSP00000384212.1
	IL18BP	ENST00000393703.9	TSL:3 MANE Select	c.-59+413A>G		intron	N/A	ENSP00000377306.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 87924 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 48732

African (AFR) AF: 0.00 AC: 0 AN: 2438

American (AMR) AF: 0.00 AC: 0 AN: 4002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2012

East Asian (EAS) AF: 0.00 AC: 0 AN: 3080

South Asian (SAS) AF: 0.00 AC: 0 AN: 17856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50802

Other (OTH) AF: 0.00 AC: 0 AN: 4166

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		-0.39
PromoterAI		0.011	Neutral

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: rs2298455; hg19: chr11-71710478;