2-112917503-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014439.4(IL37):​c.266-132A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000037 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>T		intron	N/A	NP_055254.2
	IL37	NM_173202.2		c.203-132A>T		intron	N/A	NP_775294.1	Q9NZH6-4
	IL37	NM_173205.2		c.188-132A>T		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>T		intron	N/A	ENSP00000263326.3	Q9NZH6-1
	IL37	ENST00000352179.7	TSL:1	c.203-132A>T		intron	N/A	ENSP00000263327.3	Q9NZH6-4
	IL37	ENST00000311328.2	TSL:1	c.188-132A>T		intron	N/A	ENSP00000309883.2	Q9NZH6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000370 AC: 3 AN: 811164 Hom.: 0 AF XY: 0.00000724 AC XY: 3 AN XY: 414564

African (AFR) AF: 0.00 AC: 0 AN: 19584

American (AMR) AF: 0.00 AC: 0 AN: 27236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16308

East Asian (EAS) AF: 0.00 AC: 0 AN: 35944

South Asian (SAS) AF: 0.0000357 AC: 2 AN: 56016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2618

European-Non Finnish (NFE) AF: 0.00000173 AC: 1 AN: 577206

Other (OTH) AF: 0.00 AC: 0 AN: 38082

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.051
DANN	Benign	0.48
PhyloP100		-2.6

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;