2-112980032-A-G

Variant names:

• chr2-112980032-A-G
• rs138502461
• NM_019618.4:c.184A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019618.4(IL36G):​c.184A>G​(p.Lys62Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,613,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: IL36G NM_019618.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.830
• Publications: 3 publications found

Genes affected

IL36G (HGNC:15741): (interleukin 36 gamma) The protein encoded by this gene is a member of the interleukin 1 cytokine family. The activity of this cytokine is mediated by interleukin 1 receptor-like 2 (IL1RL2/IL1R-rp2), and is specifically inhibited by interleukin 1 family, member 5 (IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha and interleukin 1, beta (IL1B) are reported to stimulate the expression of this cytokine in keratinocytes. The expression of this cytokine in keratinocytes can also be induced by a contact hypersensitivity reaction or herpes simplex virus infection. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, May 2019]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0776158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019618.4. 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
	IL36G	NM_019618.4	MANE Select	c.184A>G	p.Lys62Glu	missense	Exon 4 of 5	NP_062564.1	Q9NZH8-1
	IL36G	NM_001278568.2		c.79A>G	p.Lys27Glu	missense	Exon 3 of 4	NP_001265497.1	Q9NZH8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36G	ENST00000259205.5	TSL:1 MANE Select	c.184A>G	p.Lys62Glu	missense	Exon 4 of 5	ENSP00000259205.3	Q9NZH8-1
	IL36G	ENST00000376489.6	TSL:1	c.79A>G	p.Lys27Glu	missense	Exon 3 of 4	ENSP00000365672.2	Q9NZH8-2

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000379 AC: 95 AN: 250694 AF XY: 0.000340

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000680

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000446 AC: 652 AN: 1461348 Hom.: 0 Cov.: 30 AF XY: 0.000415 AC XY: 302 AN XY: 726986

African (AFR) AF: 0.0000598 AC: 2 AN: 33450

American (AMR) AF: 0.000314 AC: 14 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000531 AC: 590 AN: 1111732

Other (OTH) AF: 0.000530 AC: 32 AN: 60374

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74484

African (AFR) AF: 0.000168 AC: 7 AN: 41564

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000623 Hom.: 0

Bravo AF: 0.000359

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000346 AC: 42

EpiCase AF: 0.000654

EpiControl AF: 0.00101

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	-0.31	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.83
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.052	T
Polyphen		0.97	D
Vest4		0.56
MVP		0.17
MPC		0.48
ClinPred		0.11	T
GERP RS		2.3
Varity_R		0.55
gMVP		0.44
Mutation Taster		=88/12	polymorphism

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: rs138502461; hg19: chr2-113737609;