rs145021212

Variant names:

• chr2-113028963-C-G
• rs145021212
• NM_173178.3:c.237G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173178.3(IL36B):​c.237G>C​(p.Gln79His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: IL36B NM_173178.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.830
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05971402).

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.237G>C	p.Gln79His	missense	Exon 4 of 5	NP_775270.1	Q9NZH7-2
	IL36B	NM_014438.5		c.237G>C	p.Gln79His	missense	Exon 4 of 6	NP_055253.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36B	ENST00000327407.2	TSL:1 MANE Select	c.237G>C	p.Gln79His	missense	Exon 4 of 5	ENSP00000328420.2	Q9NZH7-2
	IL36B	ENST00000259213.9	TSL:1	c.237G>C	p.Gln79His	missense	Exon 4 of 6	ENSP00000259213.4	Q9NZH7-1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251292 AF XY: 0.000140

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000268 AC: 392 AN: 1461762 Hom.: 0 Cov.: 31 AF XY: 0.000267 AC XY: 194 AN XY: 727174

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000345 AC: 384 AN: 1111944

Other (OTH) AF: 0.000116 AC: 7 AN: 60390

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.83
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.041
Sift	Benign	0.098	T
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.35		Loss of ubiquitination at K81 (P = 0.0589)
MVP		0.092
MPC		0.31
ClinPred		0.17	T
GERP RS		0.40
Varity_R		0.083
gMVP		0.35
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs145021212; hg19: chr2-113786540;