chr11-71999432-A-C

Variant names:

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

Variant summary

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

The ENST00000497194.6(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 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: Benign. The variant received -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.

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>C		intron	N/A	NP_001034749.1
	IL18BP	NM_005699.3		c.-553A>C		5_prime_UTR	Exon 1 of 4	NP_005690.2
	IL18BP	NM_173042.2		c.-553A>C		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>C		5_prime_UTR	Exon 1 of 4	ENSP00000434717.1
	IL18BP	ENST00000404792.5	TSL:1	c.-553A>C		5_prime_UTR	Exon 1 of 5	ENSP00000384212.1
	IL18BP	ENST00000393703.9	TSL:3 MANE Select	c.-59+413A>C		intron	N/A	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

African (AFR) AF: 0.0900 AC: 219 AN: 2434

American (AMR) AF: 0.102 AC: 407 AN: 3996

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 289 AN: 2008

East Asian (EAS) AF: 0.252 AC: 770 AN: 3060

South Asian (SAS) AF: 0.0918 AC: 1636 AN: 17828

European-Finnish (FIN) AF: 0.111 AC: 361 AN: 3262

Middle Eastern (MID) AF: 0.106 AC: 32 AN: 302

European-Non Finnish (NFE) AF: 0.107 AC: 5434 AN: 50736

Other (OTH) AF: 0.119 AC: 494 AN: 4162

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

African (AFR) AF: 0.117 AC: 4866 AN: 41526

American (AMR) AF: 0.124 AC: 1902 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1370 AN: 5164

South Asian (SAS) AF: 0.0986 AC: 476 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10604

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8260 AN: 67998

Other (OTH) AF: 0.125 AC: 263 AN: 2112

Alfa AF: 0.120 Hom.: 2371

Bravo AF: 0.126

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.39
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298455; hg19: chr11-71710478; COSMIC: COSV107276405; COSMIC: COSV107276405;