2-112913801-GA-CT

Variant names:

• chr2-112913801-GA-CT
• NM_014439.4:c.92_93delGAinsCT
• IL37 p.Gly31Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014439.4(IL37):​c.92_93delGAinsCT​(p.Gly31Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G31V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL37 NM_014439.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.92_93delGAinsCT	p.Gly31Ala	missense	N/A	NP_055254.2
	IL37	NM_173204.2		c.92_93delGAinsCT	p.Gly31Ala	missense	N/A	NP_775296.1	Q9NZH6-3
	IL37	NM_173202.2		c.82+707_82+708delGAinsCT		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.92_93delGAinsCT	p.Gly31Ala	missense	N/A	ENSP00000263326.3	Q9NZH6-1
	IL37	ENST00000353225.7	TSL:1	c.92_93delGAinsCT	p.Gly31Ala	missense	N/A	ENSP00000309208.3	Q9NZH6-3
	IL37	ENST00000352179.7	TSL:1	c.82+707_82+708delGAinsCT		intron	N/A	ENSP00000263327.3	Q9NZH6-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-113671378;