2-112917503-A-G

Variant names:

• chr2-112917503-A-G
• rs2723186
• NM_014439.4:c.266-132A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014439.4(IL37):​c.266-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 963,232 control chromosomes in the GnomAD database, including 452,516 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (64006 hom., cov: 31)
  • Exomes 𝑓: 0.98 (388510 hom.)
• Consequence: IL37 NM_014439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	NM_014439.4	MANE Select	c.266-132A>G		intron	N/A	NP_055254.2
	IL37	NM_173202.2		c.203-132A>G		intron	N/A	NP_775294.1	Q9NZH6-4
	IL37	NM_173205.2		c.188-132A>G		intron	N/A	NP_775297.1	Q9NZH6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL37	ENST00000263326.8	TSL:1 MANE Select	c.266-132A>G		intron	N/A	ENSP00000263326.3	Q9NZH6-1
	IL37	ENST00000352179.7	TSL:1	c.203-132A>G		intron	N/A	ENSP00000263327.3	Q9NZH6-4
	IL37	ENST00000311328.2	TSL:1	c.188-132A>G		intron	N/A	ENSP00000309883.2	Q9NZH6-2

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138161 AN: 152056 Hom.: 63979 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.913

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.936

GnomAD4 exome AF: 0.977 AC: 792439 AN: 811058 Hom.: 388510 AF XY: 0.976 AC XY: 404410 AN XY: 414502

African (AFR) AF: 0.698 AC: 13654 AN: 19552

American (AMR) AF: 0.980 AC: 26697 AN: 27232

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 16054 AN: 16306

East Asian (EAS) AF: 0.862 AC: 30950 AN: 35920

South Asian (SAS) AF: 0.918 AC: 51384 AN: 55996

European-Finnish (FIN) AF: 1.00 AC: 38156 AN: 38170

Middle Eastern (MID) AF: 0.972 AC: 2544 AN: 2618

European-Non Finnish (NFE) AF: 0.998 AC: 576285 AN: 577198

Other (OTH) AF: 0.965 AC: 36715 AN: 38066

GnomAD4 genome AF: 0.908 AC: 138231 AN: 152174 Hom.: 64006 Cov.: 31 AF XY: 0.909 AC XY: 67654 AN XY: 74400

African (AFR) AF: 0.711 AC: 29478 AN: 41458

American (AMR) AF: 0.965 AC: 14764 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3417 AN: 3472

East Asian (EAS) AF: 0.869 AC: 4488 AN: 5164

South Asian (SAS) AF: 0.913 AC: 4401 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67888 AN: 68024

Other (OTH) AF: 0.937 AC: 1983 AN: 2116

Alfa AF: 0.961 Hom.: 31458

Bravo AF: 0.898

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.059
DANN	Benign	0.57
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2723186; hg19: chr2-113675080;