rs1678410208

Variant names:

• chr1-206902047-T-C
• rs1678410208
• NM_006850.3:c.512T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-206902047-T-C
• chr1-206902047-T-G

Variant summary

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

The NM_006850.3(IL24):​c.512T>C​(p.Leu171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign 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. L171R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IL24 NM_006850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• 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=0.32457453).

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.512T>C	p.Leu171Pro	missense	Exon 6 of 7	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.515T>C	p.Leu172Pro	missense	Exon 6 of 7	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.356T>C	p.Leu119Pro	missense	Exon 5 of 6	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.512T>C	p.Leu171Pro	missense	Exon 6 of 7	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.515T>C	p.Leu172Pro	missense	Exon 6 of 7	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.356T>C	p.Leu119Pro	missense	Exon 5 of 6	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460074 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726384

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110396

Other (OTH) AF: 0.00 AC: 0 AN: 60336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	0.14
Eigen_PC	Benign	0.052
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.1
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.17
Sift4G	Pathogenic	0.0	D
Vest4		0.66
MutPred		0.24		Gain of methylation at C53 (P = 0.0115)
MVP		0.59
ClinPred		0.94	D
GERP RS		2.3
Varity_R		0.81
Mutation Taster		=63/37	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

dbSNP: rs1678410208; hg19: chr1-207075392;