rs10496447

Positions:

• chr2-113024482-A-G

Variant summary

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

The NM_014438.5(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 NM_014438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL36B	NM_014438.5	c.391+1621T>C		intron_variant		ENST00000259213.9	NP_055253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL36B	ENST00000259213.9	c.391+1621T>C		intron_variant		1	NM_014438.5	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

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0692

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.120

Alfa AF: 0.137 Hom.: 1982

Bravo AF: 0.123

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10496447; hg19: chr2-113782059;