rs10496447

Variant names:

• chr2-113024482-A-G
• rs10496447
• ENST00000259213.9:c.391+1621T>C

Variant summary

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

The ENST00000259213.9(IL36B):​c.391+1621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,212 control chromosomes in the GnomAD database, including 1,171 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 0.12 (1171 hom., cov: 32)
• Consequence: IL36B ENST00000259213.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259213.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36B	NM_014438.5		c.391+1621T>C		intron	N/A	NP_055253.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36B	ENST00000259213.9	TSL:1	c.391+1621T>C		intron	N/A	ENSP00000259213.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18330 AN: 152094 Hom.: 1173 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.120 AC: 18326 AN: 152212 Hom.: 1171 Cov.: 32 AF XY: 0.117 AC XY: 8686 AN XY: 74420

African (AFR) AF: 0.116 AC: 4825 AN: 41526

American (AMR) AF: 0.105 AC: 1606 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5182

South Asian (SAS) AF: 0.130 AC: 625 AN: 4810

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10606

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9404 AN: 68012

Other (OTH) AF: 0.120 AC: 253 AN: 2108

Alfa AF: 0.133 Hom.: 4169

Bravo AF: 0.123

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10496447; hg19: chr2-113782059;