rs5743673

Positions:

• chr11-72001407-G-A
• chr11-72001407-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001039660.2(IL18BP):​c.362G>A​(p.Arg121Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,614,050 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.023 (132 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (119 hom.)
• Consequence: IL18BP NM_001039660.2 missense, splice_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 11-72001407-G-A is Benign according to our data. Variant chr11-72001407-G-A is described in ClinVar as [Benign]. Clinvar id is 787089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18BP	NM_001039660.2	c.362G>A	p.Arg121Gln	missense_variant, splice_region_variant	5/6	ENST00000393703.9	NP_001034749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000393703.9	c.362G>A	p.Arg121Gln	missense_variant, splice_region_variant	5/6	3	NM_001039660.2	ENSP00000377306.4

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3481 AN: 152188 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00575 AC: 1433 AN: 249156 Hom.: 49 AF XY: 0.00441 AC XY: 597 AN XY: 135226

Gnomad AFR exome AF: 0.0820

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00239 AC: 3491 AN: 1461742 Hom.: 119 Cov.: 32 AF XY: 0.00210 AC XY: 1526 AN XY: 727150

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.0229 AC: 3483 AN: 152308 Hom.: 132 Cov.: 32 AF XY: 0.0220 AC XY: 1641 AN XY: 74494

Gnomad4 AFR AF: 0.0797

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00337 Hom.: 31

Bravo AF: 0.0257

ESP6500AA AF: 0.0740 AC: 308

ESP6500EA AF: 0.000358 AC: 3

ExAC AF: 0.00679 AC: 821

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T;T;.;T;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.54	.;.;.;.;T;T;.;T
MetaRNN	Benign	0.0022	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;L;L;L;.;L;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N;N;N;N;.;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.064	T;T;T;T;.;T;T;T
Sift4G	Uncertain	0.040	D;T;D;D;T;T;D;D
Polyphen		0.33	B;P;B;B;.;P;B;B
Vest4		0.11
MVP		0.55
MPC		0.037
ClinPred		0.0091	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.064
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.53		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5743673; hg19: chr11-71712453;