11-72001407-G-C

Variant names:

• chr11-72001407-G-C
• NM_001039660.2:c.362G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039660.2(IL18BP):​c.362G>C​(p.Arg121Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R121Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IL18BP NM_001039660.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20314461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18BP	NM_001039660.2	c.362G>C	p.Arg121Pro	missense_variant, splice_region_variant	Exon 5 of 6	ENST00000393703.9	NP_001034749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000393703.9	c.362G>C	p.Arg121Pro	missense_variant, splice_region_variant	Exon 5 of 6	3	NM_001039660.2	ENSP00000377306.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461742 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T;T;.;T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.50	.;.;.;.;T;T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.5	L;.;L;L;L;.;L;L
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;.;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.012	D;D;D;D;.;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D;D
Polyphen		0.98	D;D;D;D;.;D;D;D
Vest4		0.41
MutPred		0.22		Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);Loss of catalytic residue at R121 (P = 0.0423);
MVP		0.65
MPC		0.042
ClinPred		0.70	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.61
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71712453;