chr2-112913816-C-A

Variant names:

• chr2-112913816-C-A
• rs372712283
• NM_014439.4:c.107C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014439.4(IL37):​c.107C>A​(p.Pro36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,572 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: IL37 NM_014439.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.110
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021783024).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	NM_014439.4	MANE Select	c.107C>A	p.Pro36Gln	missense	Exon 3 of 6	NP_055254.2
	IL37	NM_173204.2		c.107C>A	p.Pro36Gln	missense	Exon 3 of 5	NP_775296.1	Q9NZH6-3
	IL37	NM_173202.2		c.82+722C>A		intron	N/A	NP_775294.1	Q9NZH6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	ENST00000263326.8	TSL:1 MANE Select	c.107C>A	p.Pro36Gln	missense	Exon 3 of 6	ENSP00000263326.3	Q9NZH6-1
	IL37	ENST00000353225.7	TSL:1	c.107C>A	p.Pro36Gln	missense	Exon 2 of 4	ENSP00000309208.3	Q9NZH6-3
	IL37	ENST00000352179.7	TSL:1	c.82+722C>A		intron	N/A	ENSP00000263327.3	Q9NZH6-4

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152154 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251058 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1461418 Hom.: 0 Cov.: 45 AF XY: 0.0000303 AC XY: 22 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00110 AC: 49 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111636

Other (OTH) AF: 0.0000994 AC: 6 AN: 60380

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152154 Hom.: 1 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00137 AC: 21 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000276

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000157 AC: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.067
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.18
MVP		0.27
MPC		0.093
ClinPred		0.027	T
GERP RS		-0.53
Varity_R		0.078
gMVP		0.079
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs372712283; hg19: chr2-113671393; COSMIC: COSV99636052; COSMIC: COSV99636052;