1-206902976-T-G

Variant names:

• chr1-206902976-T-G
• rs150080259
• NM_006850.3:c.538T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 14/22 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
• Publications: 9 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.538T>G	p.Leu180Val	missense splice_region	Exon 7 of 7	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.541T>G	p.Leu181Val	missense splice_region	Exon 7 of 7	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.382T>G	p.Leu128Val	missense splice_region	Exon 6 of 6	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.538T>G	p.Leu180Val	missense splice_region	Exon 7 of 7	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.541T>G	p.Leu181Val	missense splice_region	Exon 7 of 7	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.382T>G	p.Leu128Val	missense splice_region	Exon 6 of 6	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 298 AN: 152194 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00334 AC: 837 AN: 250790 AF XY: 0.00360

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 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.: 29 Cov.: 33 AF XY: 0.00266 AC XY: 1932 AN XY: 727234

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.000894 AC: 40 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00520 AC: 136 AN: 26136

East Asian (EAS) AF: 0.0176 AC: 697 AN: 39698

South Asian (SAS) AF: 0.00806 AC: 695 AN: 86254

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00174 AC: 1935 AN: 1111992

Other (OTH) AF: 0.00316 AC: 191 AN: 60394

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152312 Hom.: 2 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74480

African (AFR) AF: 0.000265 AC: 11 AN: 41556

American (AMR) AF: 0.00131 AC: 20 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5186

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68016

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00202 Hom.: 4

Bravo AF: 0.00164

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00357 AC: 433

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.39	T
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	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.63
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.23
Sift	Uncertain	0.020	D
Sift4G	Benign	0.072	T
Polyphen		0.90	P
Vest4		0.39
MVP		0.27
MPC		0.30
ClinPred		0.042	T
GERP RS		-0.76
Varity_R		0.28
gMVP		0.35
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs150080259; hg19: chr1-207076321;