NM_006850.3:c.29T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006850.3(IL24):c.29T>C(p.Leu10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,607,150 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.015 ( 63 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 67 hom. )

Consequence

IL24
NM_006850.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.37

Publications

6 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023302138).

BP6

Variant 1-206897861-T-C is Benign according to our data. Variant chr1-206897861-T-C is described in ClinVar as Benign. ClinVar VariationId is 727218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL24	NM_006850.3	MANE Select	c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	NP_006841.1	Q13007-1
IL24	NM_001185156.1		c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	NP_001172085.1	Q13007-2
IL24	NM_001185157.1		c.29T>C	p.Leu10Pro	missense	Exon 2 of 6	NP_001172086.1	Q13007-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL24	ENST00000294984.7	TSL:1 MANE Select	c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	ENSP00000294984.2	Q13007-1
IL24	ENST00000391929.7	TSL:1	c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	ENSP00000375795.3	Q13007-2
IL24	ENST00000367093.3	TSL:1	c.29T>C	p.Leu10Pro	missense	Exon 2 of 6	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2258

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00401

AC:

960

AN:

239354

AF XY:

0.00292

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.00317

Gnomad ASJ exome

AF:

0.00264

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.00152

GnomAD4 exome

AF:

0.00175

AC:

2551

AN:

1454928

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1108

AN XY:

722910

show subpopulations

African (AFR)

AF:

0.0550

AC:

1836

AN:

33382

American (AMR)

AF:

0.00395

AC:

174

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.00215

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.0000945

AC:

AN:

84656

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52872

Middle Eastern (MID)

AF:

0.00587

AC:

AN:

4766

European-Non Finnish (NFE)

AF:

0.000183

AC:

203

AN:

1109438

Other (OTH)

AF:

0.00408

AC:

245

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

108

215

323

430

538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0149

AC:

2264

AN:

152222

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1060

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0505

AC:

2097

AN:

41524

American (AMR)

AF:

0.00654

AC:

100

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68004

Other (OTH)

AF:

0.0137

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.0171

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0472

AC:

208

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00477

AC:

579

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-0.79

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-1.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.12

REVEL

Benign

0.090

Sift

Benign

0.036

Sift4G

Uncertain

0.0090

Polyphen

0.95

Vest4

0.41

MVP

0.14

MPC

0.54

ClinPred

0.031

GERP RS

-2.2

PromoterAI

-0.0090

Neutral

(source)

Varity_R

0.17

gMVP

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over