2-112917258-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014439.4(IL37):c.265+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,132 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: IL37 NM_014439.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.616

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-112917258-A-C is Benign according to our data. Variant chr2-112917258-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 782238.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL37	NM_014439.4	c.265+10A>C		intron_variant		ENST00000263326.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL37	ENST00000263326.8	c.265+10A>C		intron_variant		1	NM_014439.4	P1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00122 AC: 305 AN: 250858 Hom.: 0 AF XY: 0.00133 AC XY: 180 AN XY: 135544

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000687

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00207 AC: 3024 AN: 1460902 Hom.: 3 Cov.: 31 AF XY: 0.00198 AC XY: 1437 AN XY: 726766

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000929

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74428

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00134

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.2
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs139354551; hg19: chr2-113674835;