1-206901560-T-C

Position:

• chr1-206901560-T-C

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.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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (12397 hom., cov: 31)
  • Exomes 𝑓: 0.44 (144167 hom.)
• Consequence: IL24 NM_006850.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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 (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 id 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/exons	MANE	UniProt
IL24	NM_006850.3	c.370T>C	p.Tyr124His	missense_variant	5/7	ENST00000294984.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL24	ENST00000294984.7	c.370T>C	p.Tyr124His	missense_variant	5/7	1	NM_006850.3	P4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59878 AN: 151972 Hom.: 12391 Cov.: 31

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

GnomAD3 exomes AF: 0.402 AC: 100973 AN: 251178 Hom.: 21498 AF XY: 0.399 AC XY: 54152 AN XY: 135774

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 SAS exome AF: 0.250

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.: 37 AF XY: 0.434 AC XY: 315677 AN XY: 727036

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.394 AC: 59922 AN: 152090 Hom.: 12397 Cov.: 31 AF XY: 0.388 AC XY: 28837 AN XY: 74352

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.441

Alfa AF: 0.454 Hom.: 40023

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

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 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	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.0098
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	.;M
MutationTaster	Benign	0.73	P;P;P
PrimateAI	Uncertain	0.54	T
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	T
GERP RS		2.4
Varity_R		0.38
gMVP		0.45

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: rs1150258; hg19: chr1-207074905; COSMIC: COSV54321799; COSMIC: COSV54321799;