rs2298455

Positions:

• chr11-71999432-A-C
• chr11-71999432-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005699.3(IL18BP):​c.-553A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 240,002 control chromosomes in the GnomAD database, including 1,978 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 0.13 (1303 hom., cov: 32)
  • Exomes 𝑓: 0.11 (675 hom.)
• Consequence: IL18BP NM_005699.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18BP	NM_001039660.2	c.-59+413A>C		intron_variant		ENST00000393703.9	NP_001034749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000393703.9	c.-59+413A>C		intron_variant		3	NM_001039660.2	ENSP00000377306.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19021 AN: 152096 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.110 AC: 9642 AN: 87788 Hom.: 675 Cov.: 0 AF XY: 0.109 AC XY: 5279 AN XY: 48652

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.125 AC: 19053 AN: 152214 Hom.: 1303 Cov.: 32 AF XY: 0.124 AC XY: 9247 AN XY: 74430

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.125

Alfa AF: 0.109 Hom.: 578

Bravo AF: 0.126

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2298455; hg19: chr11-71710478;