rs5743658

Positions:

• chr11-71998678-A-C

Variant summary

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

The ENST00000497194(IL18BP):​c.-1307A>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 0.126 in 153,162 control chromosomes in the GnomAD database, including 2,749 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 (2747 hom., cov: 32)
  • Exomes 𝑓: 0.033 (2 hom.)
• Consequence: IL18BP ENST00000497194 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.71998678A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000497194	c.-1307A>C		5_prime_UTR_variant	1/4	1		ENSP00000434717.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19153 AN: 151984 Hom.: 2724 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0972

GnomAD4 exome AF: 0.0330 AC: 35 AN: 1060 Hom.: 2 Cov.: 0 AF XY: 0.0361 AC XY: 23 AN XY: 638

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.0204

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0323

GnomAD4 genome AF: 0.126 AC: 19223 AN: 152102 Hom.: 2747 Cov.: 32 AF XY: 0.123 AC XY: 9116 AN XY: 74376

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0472

Gnomad4 EAS AF: 0.0735

Gnomad4 SAS AF: 0.0432

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0578 Hom.: 772

Bravo AF: 0.140

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743658; hg19: chr11-71709724;