rs2723176

chr2-112914932-A-Cchr2-112914932-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
IL37	NM_014439.4	c.145+1078A>C		intron_variant		ENST00000263326.8
IL37	NM_173202.2	c.82+1838A>C		intron_variant
IL37	NM_173203.2	c.82+1838A>C		intron_variant
IL37	NM_173204.2	c.145+1078A>C		intron_variant

Ensembl

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

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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.938

Alfa AF: 0.936 Hom.: 4802

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

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;