2-113033616-C-T

Variant names:

• chr2-113033616-C-T
• rs6758965
• NM_173178.3:c.-57-1850G>A

Variant summary

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

The NM_173178.3(IL36B):​c.-57-1850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,962 control chromosomes in the GnomAD database, including 19,446 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 0.50 (19446 hom., cov: 32)
• Consequence: IL36B NM_173178.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173178.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36B	NM_173178.3	MANE Select	c.-57-1850G>A		intron	N/A	NP_775270.1	Q9NZH7-2
	IL36B	NM_014438.5		c.-57-1850G>A		intron	N/A	NP_055253.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36B	ENST00000327407.2	TSL:1 MANE Select	c.-57-1850G>A		intron	N/A	ENSP00000328420.2	Q9NZH7-2
	IL36B	ENST00000259213.9	TSL:1	c.-57-1850G>A		intron	N/A	ENSP00000259213.4	Q9NZH7-1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76196 AN: 151842 Hom.: 19423 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.502 AC: 76256 AN: 151962 Hom.: 19446 Cov.: 32 AF XY: 0.510 AC XY: 37869 AN XY: 74272

African (AFR) AF: 0.464 AC: 19199 AN: 41414

American (AMR) AF: 0.554 AC: 8458 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2060 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3578 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3210 AN: 4822

European-Finnish (FIN) AF: 0.556 AC: 5855 AN: 10540

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32242 AN: 67970

Other (OTH) AF: 0.537 AC: 1130 AN: 2106

Alfa AF: 0.489 Hom.: 25357

Bravo AF: 0.501

Asia WGS AF: 0.666 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6758965; hg19: chr2-113791193; COSMIC: COSV52085193;