Genetic Variant IL24:p.Tyr124His (chr1-206901560-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006850.3(IL24):c.370T>C(p.Tyr124His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,613,506 control chromosomes in the GnomAD database, including 156,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12397 hom., cov: 31)

Exomes 𝑓: 0.44 ( 144167 hom. )

Consequence

IL24
NM_006850.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

Publications

41 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019120872).

BP6

Variant 1-206901560-T-C is Benign according to our data. Variant chr1-206901560-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688384.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL24	NM_006850.3 link	c.370T>C	p.Tyr124His	missense_variant	Exon 5 of 7	ENST00000294984.7	NP_006841.1	Q13007-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL24	ENST00000294984.7 link	c.370T>C	p.Tyr124His	missense_variant	Exon 5 of 7	1	NM_006850.3	ENSP00000294984.2		Q13007-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59878

AN:

151972

Hom.:

12391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.437

GnomAD2 exomes

AF:

0.402

AC:

100973

AN:

251178

AF XY:

0.399

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.462

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.438

AC:

640821

AN:

1461416

Hom.:

144167

Cov.:

AF XY:

0.434

AC XY:

315677

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.285

AC:

9524

AN:

33456

American (AMR)

AF:

0.458

AC:

20461

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12662

AN:

26124

East Asian (EAS)

AF:

0.248

AC:

9844

AN:

39674

South Asian (SAS)

AF:

0.252

AC:

21770

AN:

86224

European-Finnish (FIN)

AF:

0.387

AC:

20656

AN:

53412

Middle Eastern (MID)

AF:

0.489

AC:

2815

AN:

5760

European-Non Finnish (NFE)

AF:

0.465

AC:

517459

AN:

1111704

Other (OTH)

AF:

0.424

AC:

25630

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18075

36150

54225

72300

90375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15126

30252

45378

60504

75630

<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:

0.394

AC:

59922

AN:

152090

Hom.:

12397

Cov.:

AF XY:

0.388

AC XY:

28837

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.290

AC:

12022

AN:

41492

American (AMR)

AF:

0.440

AC:

6731

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1635

AN:

3470

East Asian (EAS)

AF:

0.226

AC:

1171

AN:

5180

South Asian (SAS)

AF:

0.239

AC:

1151

AN:

4818

European-Finnish (FIN)

AF:

0.378

AC:

3996

AN:

10564

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31741

AN:

67960

Other (OTH)

AF:

0.441

AC:

932

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1816

3633

5449

7266

9082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.447

Hom.:

70038

Bravo

AF:

0.395

TwinsUK

AF:

0.464

AC:

1720

ALSPAC

AF:

0.453

AC:

1746

ESP6500AA

AF:

0.296

AC:

1303

ESP6500EA

AF:

0.472

AC:

4055

ExAC

AF:

0.397

AC:

48249

Asia WGS

AF:

0.257

AC:

893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 57. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.0098

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

.;M

PhyloP100

1.1

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.10

Sift

Benign

0.098

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.15

MPC

0.55

ClinPred

0.029

GERP RS

2.4

Varity_R

0.38

gMVP

0.45

Mutation Taster

=91/9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over