2-112913801-G-T

Variant names:

• chr2-112913801-G-T
• rs3811046
• NM_014439.4:c.92G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014439.4(IL37):​c.92G>T​(p.Gly31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,610,358 control chromosomes in the GnomAD database, including 393,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (30082 hom., cov: 32)
  • Exomes 𝑓: 0.70 (363133 hom.)
• Consequence: IL37 NM_014439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 55 publications found

Genes affected

IL37 (HGNC:15563): (interleukin 37) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18. This gene along with eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

IL37 Gene-Disease associations (from GenCC):

• inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	NM_014439.4	MANE Select	c.92G>T	p.Gly31Val	missense	Exon 3 of 6	NP_055254.2
	IL37	NM_173204.2		c.92G>T	p.Gly31Val	missense	Exon 3 of 5	NP_775296.1
	IL37	NM_173202.2		c.82+707G>T		intron	N/A	NP_775294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	ENST00000263326.8	TSL:1 MANE Select	c.92G>T	p.Gly31Val	missense	Exon 3 of 6	ENSP00000263326.3
	IL37	ENST00000353225.7	TSL:1	c.92G>T	p.Gly31Val	missense	Exon 2 of 4	ENSP00000309208.3
	IL37	ENST00000352179.7	TSL:1	c.82+707G>T		intron	N/A	ENSP00000263327.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90359 AN: 151966 Hom.: 30065 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.631

GnomAD2 exomes AF: 0.707 AC: 176516 AN: 249698 AF XY: 0.711

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.727

Gnomad EAS exome AF: 0.828

Gnomad FIN exome AF: 0.727

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.701 AC: 1021735 AN: 1458274 Hom.: 363133 Cov.: 43 AF XY: 0.702 AC XY: 509086 AN XY: 725480

African (AFR) AF: 0.248 AC: 8290 AN: 33410

American (AMR) AF: 0.830 AC: 37058 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18903 AN: 26060

East Asian (EAS) AF: 0.814 AC: 32242 AN: 39624

South Asian (SAS) AF: 0.732 AC: 62991 AN: 86026

European-Finnish (FIN) AF: 0.719 AC: 38343 AN: 53300

Middle Eastern (MID) AF: 0.631 AC: 3635 AN: 5760

European-Non Finnish (NFE) AF: 0.702 AC: 778584 AN: 1109198

Other (OTH) AF: 0.692 AC: 41689 AN: 60270

GnomAD4 genome AF: 0.594 AC: 90402 AN: 152084 Hom.: 30082 Cov.: 32 AF XY: 0.602 AC XY: 44774 AN XY: 74354

African (AFR) AF: 0.270 AC: 11187 AN: 41466

American (AMR) AF: 0.746 AC: 11399 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2484 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4255 AN: 5168

South Asian (SAS) AF: 0.725 AC: 3498 AN: 4824

European-Finnish (FIN) AF: 0.725 AC: 7668 AN: 10572

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47760 AN: 67974

Other (OTH) AF: 0.632 AC: 1335 AN: 2112

Alfa AF: 0.662 Hom.: 102311

Bravo AF: 0.583

TwinsUK AF: 0.714 AC: 2646

ALSPAC AF: 0.699 AC: 2693

ESP6500AA AF: 0.280 AC: 1234

ESP6500EA AF: 0.707 AC: 6080

ExAC AF: 0.689 AC: 83670

Asia WGS AF: 0.736 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.12
Sift	Benign	0.21	T
Sift4G	Benign	0.16	T
Polyphen		0.87	P
Vest4		0.074
MPC		0.11
ClinPred		0.013	T
GERP RS		1.9
Varity_R		0.078
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: -9

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

Other links and lift over

dbSNP: rs3811046; hg19: chr2-113671378; COSMIC: COSV54490353; COSMIC: COSV54490353;