rs1150258

Positions:

• chr1-206901560-T-A
• chr1-206901560-T-C
• chr1-206901560-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006850.3(IL24):​c.370T>A​(p.Tyr124Asn) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y124H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: IL24 NM_006850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

IL24 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL24	NM_006850.3	c.370T>A	p.Tyr124Asn	missense_variant	5/7	ENST00000294984.7	NP_006841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL24	ENST00000294984.7	c.370T>A	p.Tyr124Asn	missense_variant	5/7	1	NM_006850.3	ENSP00000294984.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	.;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.60
MutPred		0.43		.;Gain of disorder (P = 0.0537);
MVP		0.38
MPC		0.62
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.76
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1150258; hg19: chr1-207074905;