rs1150258

Variant names:

• chr1-206901560-T-C
• rs1150258
• NM_006850.3:c.370T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-206901560-T-C
• chr1-206901560-T-A
• chr1-206901560-T-G

Variant summary

Our verdict is Benign. The variant received -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 (★).

• 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
• Publications: 41 publications found

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

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL24	NM_006850.3	MANE Select	c.370T>C	p.Tyr124His	missense	Exon 5 of 7	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.373T>C	p.Tyr125His	missense	Exon 5 of 7	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.307-438T>C		intron	N/A	NP_001172086.1	Q13007-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL24	ENST00000294984.7	TSL:1 MANE Select	c.370T>C	p.Tyr124His	missense	Exon 5 of 7	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.373T>C	p.Tyr125His	missense	Exon 5 of 7	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.307-438T>C		intron	N/A	ENSP00000356060.3	Q13007-3

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

GnomAD2 exomes AF: 0.402 AC: 100973 AN: 251178 AF XY: 0.399

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

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

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

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.10
Sift	Benign	0.098	T
Sift4G	Pathogenic	0.0	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
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

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