chr2-112914932-A-C

Variant names:

• chr2-112914932-A-C
• rs2723176
• NM_014439.4:c.145+1078A>C

Variant summary

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

The NM_014439.4(IL37):​c.145+1078A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,200 control chromosomes in the GnomAD database, including 64,020 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 (64020 hom., cov: 32)
• Consequence: IL37 NM_014439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL37	NM_014439.4	c.145+1078A>C		intron_variant	Intron 3 of 5	ENST00000263326.8	NP_055254.2
IL37	NM_173202.2	c.82+1838A>C		intron_variant	Intron 2 of 4		NP_775294.1
IL37	NM_173204.2	c.145+1078A>C		intron_variant	Intron 3 of 4		NP_775296.1
IL37	NM_173203.2	c.82+1838A>C		intron_variant	Intron 2 of 3		NP_775295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL37	ENST00000263326.8	c.145+1078A>C		intron_variant	Intron 3 of 5	1	NM_014439.4	ENSP00000263326.3
IL37	ENST00000352179.7	c.82+1838A>C		intron_variant	Intron 1 of 3	1		ENSP00000263327.3
IL37	ENST00000353225.7	c.145+1078A>C		intron_variant	Intron 2 of 3	1		ENSP00000309208.3
IL37	ENST00000349806.7	c.82+1838A>C		intron_variant	Intron 1 of 2	1		ENSP00000263328.3

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138187 AN: 152082 Hom.: 63992 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.911

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.908 AC: 138257 AN: 152200 Hom.: 64020 Cov.: 32 AF XY: 0.909 AC XY: 67650 AN XY: 74394

African (AFR) AF: 0.711 AC: 29497 AN: 41464

American (AMR) AF: 0.965 AC: 14764 AN: 15302

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

East Asian (EAS) AF: 0.869 AC: 4491 AN: 5170

South Asian (SAS) AF: 0.911 AC: 4397 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

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

European-Non Finnish (NFE) AF: 0.998 AC: 67893 AN: 68034

Other (OTH) AF: 0.938 AC: 1980 AN: 2112

Alfa AF: 0.922 Hom.: 5016

Bravo AF: 0.898

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.46
PhyloP100		-0.40
PromoterAI		0.0046	Neutral
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: rs2723176; hg19: chr2-113672509;