rs1900287

chr2-113039988-G-Achr2-113039988-G-Cchr2-113039988-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014438.5(IL36B):c.-57-8222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,202 control chromosomes in the GnomAD database, including 48,009 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 0.79 (48009 hom., cov: 33)
• Consequence: IL36B NM_014438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707

Genes affected

IL36B (HGNC:15564): (interleukin 36 beta) The protein encoded by this gene is a member of the interleukin 1 cytokine family. Protein structure modeling indicated that this cytokine may contain a 12-stranded beta-trefoil structure that is conserved between IL1A (IL-A alpha) and IL1B (IL-1 beta). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL36B	NM_014438.5	c.-57-8222C>T		intron_variant		ENST00000259213.9
IL36B	NM_173178.3	c.-57-8222C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL36B	ENST00000259213.9	c.-57-8222C>T		intron_variant		1	NM_014438.5
IL36B	ENST00000327407.2	c.-57-8222C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119544 AN: 152086 Hom.: 47952 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.786 AC: 119661 AN: 152202 Hom.: 48009 Cov.: 33 AF XY: 0.794 AC XY: 59045 AN XY: 74392

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.790

Alfa AF: 0.764 Hom.: 7919

Bravo AF: 0.795

Asia WGS AF: 0.934 AC: 3245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.5
Dann	Benign	0.56

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: rs1900287; hg19: chr2-113797565;