1-206901531-A-T

Variant names:

• chr1-206901531-A-T
• NM_006850.3:c.341A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006850.3(IL24):​c.341A>T​(p.Glu114Val) 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. 14/22 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. E114K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL24 NM_006850.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

IL24 (HGNC:11346): (interleukin 24) This gene encodes a member of the IL10 family of cytokines. It was identified as a gene induced during terminal differentiation in melanoma cells. The protein encoded by this gene can induce apoptosis selectively in various cancer cells. Overexpression of this gene leads to elevated expression of several GADD family genes, which correlates with the induction of apoptosis. The phosphorylation of mitogen-activated protein kinase 14 (MAPK7/P38), and heat shock 27kDa protein 1 (HSPB2/HSP27) are found to be induced by this gene in melanoma cells, but not in normal immortal melanocytes. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2996009).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006850.3. 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
	IL24	NM_006850.3	MANE Select	c.341A>T	p.Glu114Val	missense	Exon 5 of 7	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.344A>T	p.Glu115Val	missense	Exon 5 of 7	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.307-467A>T		intron	N/A	NP_001172086.1	Q13007-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL24	ENST00000294984.7	TSL:1 MANE Select	c.341A>T	p.Glu114Val	missense	Exon 5 of 7	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.344A>T	p.Glu115Val	missense	Exon 5 of 7	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.307-467A>T		intron	N/A	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.27
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.5
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.051
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.045	D
Polyphen		0.74	P
Vest4		0.33
MutPred		0.45		Gain of MoRF binding (P = 0.1565)
MVP		0.58
MPC		0.25
ClinPred		0.70	D
GERP RS		2.4
Varity_R		0.39
gMVP		0.33
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-207074876;