chr11-71999989-CCAT-C

Variant names:

• chr11-71999989-CCAT-C
• NM_001039660.2:c.6_8delCAT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001039660.2(IL18BP):​c.6_8delCAT​(p.Met3del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL18BP NM_001039660.2 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.128
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001039660.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039660.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18BP	NM_001039660.2	MANE Select	c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 2 of 6	NP_001034749.1	O95998-2
	IL18BP	NM_005699.3		c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 1 of 4	NP_005690.2	G3V1C5
	IL18BP	NM_001039659.2		c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 3 of 7	NP_001034748.1	O95998-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18BP	ENST00000393703.9	TSL:3 MANE Select	c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 2 of 6	ENSP00000377306.4	O95998-2
	IL18BP	ENST00000497194.6	TSL:1	c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 1 of 4	ENSP00000434717.1	G3V1C5
	IL18BP	ENST00000393705.8	TSL:1	c.6_8delCAT	p.Met3del	disruptive_inframe_deletion	Exon 3 of 7	ENSP00000377308.4	O95998-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

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

hg19: chr11-71711035;