chr1-206866546-A-C

Variant names:

• chr1-206866546-A-C
• NM_018724.4:c.288A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018724.4(IL20):​c.288A>C​(p.Lys96Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K96I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL20 NM_018724.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.172
• Publications: 0 publications found

Genes affected

IL20 (HGNC:6002): (interleukin 20) The protein encoded by this gene is a cytokine structurally related to interleukin 10 (IL10). This cytokine has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role for this protein in epidermal function and psoriasis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25340325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018724.4. 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
	IL20	NM_018724.4	MANE Select	c.288A>C	p.Lys96Asn	missense	Exon 4 of 6	NP_061194.2
	IL20	NM_001385166.1		c.288A>C	p.Lys96Asn	missense	Exon 5 of 7	NP_001372095.1	Q9NYY1-1
	IL20	NM_001385167.1		c.288A>C	p.Lys96Asn	missense	Exon 6 of 8	NP_001372096.1	Q9NYY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20	ENST00000367098.6	TSL:1 MANE Select	c.288A>C	p.Lys96Asn	missense	Exon 4 of 6	ENSP00000356065.1	Q9NYY1-1
	IL20	ENST00000367096.7	TSL:1	c.288A>C	p.Lys96Asn	missense	Exon 3 of 5	ENSP00000356063.3	Q9NYY1-1
	IL20	ENST00000391930.3	TSL:1	c.288A>C	p.Lys96Asn	missense	Exon 3 of 4	ENSP00000375796.2	Q9NYY1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.17
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.090
Sift	Benign	0.086	T
Sift4G	Benign	0.20	T
Polyphen		0.046	B
Vest4		0.40
MutPred		0.57		Loss of methylation at K96 (P = 0.0011)
MVP		0.48
MPC		0.17
ClinPred		0.36	T
GERP RS		-4.1
Varity_R		0.33
gMVP		0.31
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-207039891;