NM_001039660.2:c.19T>G

Variant names:

• chr11-72000003-T-G
• rs373223475
• NM_001039660.2:c.19T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039660.2(IL18BP):​c.19T>G​(p.Trp7Gly) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W7R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL18BP NM_001039660.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40913415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18BP	NM_001039660.2	c.19T>G	p.Trp7Gly	missense_variant	Exon 2 of 6	ENST00000393703.9	NP_001034749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000393703.9	c.19T>G	p.Trp7Gly	missense_variant	Exon 2 of 6	3	NM_001039660.2	ENSP00000377306.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T;T;T;T;.;T;T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.66	.;.;.;.;T;T;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;L;L;L;.;L;L;L
PhyloP100		-0.42
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;.;D;D;D;D
REVEL	Benign	0.094
Sift	Benign	0.035	D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D;D;D;D
Polyphen		0.84	P;P;P;P;.;P;P;P;P
Vest4		0.39
MutPred		0.62		Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP		0.54
MPC		0.14
ClinPred		0.90	D
GERP RS		0.44
PromoterAI		0.024	Neutral
Varity_R		0.38
gMVP		0.23
Mutation Taster		=95/5	polymorphism

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: rs373223475; hg19: chr11-71711049;