1-206899614-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006850.3(IL24):c.240+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 981,556 control chromosomes in the GnomAD database, including 94,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12369 hom., cov: 32)
  • Exomes 𝑓: 0.44 (81857 hom.)
• Consequence: IL24 NM_006850.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-206899614-C-T is Benign according to our data. Variant chr1-206899614-C-T is described in ClinVar as [Benign]. Clinvar id is 2688458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL24	NM_006850.3	c.240+99C>T		intron_variant		ENST00000294984.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL24	ENST00000294984.7	c.240+99C>T		intron_variant		1	NM_006850.3	P4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59819 AN: 151936 Hom.: 12364 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.226

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

GnomAD4 exome AF: 0.438 AC: 363428 AN: 829502 Hom.: 81857 AF XY: 0.434 AC XY: 181016 AN XY: 417446

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.394 AC: 59863 AN: 152054 Hom.: 12369 Cov.: 32 AF XY: 0.388 AC XY: 28793 AN XY: 74302

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.441

Alfa AF: 0.461 Hom.: 16074

Bravo AF: 0.395

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.1
Dann	Benign	0.67

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: rs1150255; hg19: chr1-207072959; COSMIC: COSV54321814; COSMIC: COSV54321814;