2-112914932-A-G

Position:

• chr2-112914932-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014439.4(IL37):​c.145+1078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000526 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 32)
• Consequence: IL37 NM_014439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL37	NM_014439.4	c.145+1078A>G		intron_variant		ENST00000263326.8	NP_055254.2
IL37	NM_173202.2	c.82+1838A>G		intron_variant			NP_775294.1
IL37	NM_173203.2	c.82+1838A>G		intron_variant			NP_775295.1
IL37	NM_173204.2	c.145+1078A>G		intron_variant			NP_775296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL37	ENST00000263326.8	c.145+1078A>G		intron_variant		1	NM_014439.4	ENSP00000263326	P1
IL37	ENST00000349806.7	c.82+1838A>G		intron_variant		1		ENSP00000263328
IL37	ENST00000352179.7	c.82+1838A>G		intron_variant		1		ENSP00000263327
IL37	ENST00000353225.7	c.145+1078A>G		intron_variant		1		ENSP00000309208

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74412

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2723176; hg19: chr2-113672509;