11-72001407-G-A

Variant names:

• chr11-72001407-G-A
• rs5743673
• NM_001039660.2:c.362G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R121W) has been classified as Uncertain significance.

• 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
• Publications: 13 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: Benign. The variant received -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 11-72001407-G-A is Benign according to our data. Variant chr11-72001407-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.362G>A	p.Arg121Gln	missense splice_region	Exon 5 of 6	NP_001034749.1	O95998-2
	IL18BP	NM_005699.3		c.362G>A	p.Arg121Gln	missense splice_region	Exon 4 of 4	NP_005690.2	G3V1C5
	IL18BP	NM_001039659.2		c.362G>A	p.Arg121Gln	missense splice_region	Exon 6 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.362G>A	p.Arg121Gln	missense splice_region	Exon 5 of 6	ENSP00000377306.4	O95998-2
	IL18BP	ENST00000497194.6	TSL:1	c.362G>A	p.Arg121Gln	missense splice_region	Exon 4 of 4	ENSP00000434717.1	G3V1C5
	IL18BP	ENST00000393705.8	TSL:1	c.362G>A	p.Arg121Gln	missense splice_region	Exon 6 of 7	ENSP00000377308.4	O95998-2

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

GnomAD2 exomes AF: 0.00575 AC: 1433 AN: 249156 AF XY: 0.00441

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 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

African (AFR) AF: 0.0867 AC: 2902 AN: 33480

American (AMR) AF: 0.00385 AC: 172 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5766

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111910

Other (OTH) AF: 0.00520 AC: 314 AN: 60394

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

African (AFR) AF: 0.0797 AC: 3309 AN: 41544

American (AMR) AF: 0.00784 AC: 120 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68020

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00797 Hom.: 87

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.9
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.045
Sift	Benign	0.064	T
Sift4G	Uncertain	0.040	D
Polyphen		0.33	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5743673; hg19: chr11-71712453;