1-206902976-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006850.3(IL24):c.538T>G(p.Leu180Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,614,172 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 29 hom. )

Consequence

IL24
NM_006850.3 missense, splice_region

Scores

Splicing: ADA: 0.0001269

Clinical Significance

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

Conservation

PhyloP100: -0.633

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005724877).

BP6

Variant 1-206902976-T-G is Benign according to our data. Variant chr1-206902976-T-G is described in ClinVar as [Benign]. Clinvar id is 770860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00196 (298/152312) while in subpopulation EAS AF= 0.0224 (116/5186). AF 95% confidence interval is 0.0191. There are 2 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL24	NM_006850.3 link	c.538T>G	p.Leu180Val	missense_variant, splice_region_variant	Exon 7 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.538T>G	p.Leu180Val	missense_variant, splice_region_variant	Exon 7 of 7	1	NM_006850.3	ENSP00000294984.2		Q13007-1

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

298

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0223

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00334

AC:

837

AN:

250790

Hom.:

AF XY:

0.00360

AC XY:

488

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.0194

Gnomad SAS exome

AF:

0.00725

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00254

AC:

3715

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1932

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00520

Gnomad4 EAS exome

AF:

0.0176

Gnomad4 SAS exome

AF:

0.00806

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00196

AC:

298

AN:

152312

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.00164

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00357

AC:

433

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

.;T;.

Eigen

Benign

0.042

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.020

D;D;D

Sift4G

Benign

0.072

T;T;T

Polyphen

0.90

.;P;.

Vest4

0.39

MVP

0.27

MPC

0.30

ClinPred

0.042

GERP RS

-0.76

Varity_R

0.28

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.052

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over