rs75762018

Variant names:

• chr1-206897861-T-C
• rs75762018
• NM_006850.3:c.29T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-206897861-T-C
• chr1-206897861-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006850.3(IL24):​c.29T>C​(p.Leu10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,607,150 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.015 (63 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (67 hom.)
• Consequence: IL24 NM_006850.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37
• Publications: 6 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=0.0023302138).
• BP6: Variant 1-206897861-T-C is Benign according to our data. Variant chr1-206897861-T-C is described in ClinVar as Benign. ClinVar VariationId is 727218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 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.29T>C	p.Leu10Pro	missense	Exon 2 of 7	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.29T>C	p.Leu10Pro	missense	Exon 2 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.29T>C	p.Leu10Pro	missense	Exon 2 of 7	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.29T>C	p.Leu10Pro	missense	Exon 2 of 7	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.29T>C	p.Leu10Pro	missense	Exon 2 of 6	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2258 AN: 152104 Hom.: 63 Cov.: 31

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00401 AC: 960 AN: 239354 AF XY: 0.00292

Gnomad AFR exome AF: 0.0520

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00264

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000305

Gnomad OTH exome AF: 0.00152

GnomAD4 exome AF: 0.00175 AC: 2551 AN: 1454928 Hom.: 67 Cov.: 30 AF XY: 0.00153 AC XY: 1108 AN XY: 722910

African (AFR) AF: 0.0550 AC: 1836 AN: 33382

American (AMR) AF: 0.00395 AC: 174 AN: 44036

Ashkenazi Jewish (ASJ) AF: 0.00215 AC: 56 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.0000945 AC: 8 AN: 84656

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52872

Middle Eastern (MID) AF: 0.00587 AC: 28 AN: 4766

European-Non Finnish (NFE) AF: 0.000183 AC: 203 AN: 1109438

Other (OTH) AF: 0.00408 AC: 245 AN: 60122

GnomAD4 genome AF: 0.0149 AC: 2264 AN: 152222 Hom.: 63 Cov.: 31 AF XY: 0.0142 AC XY: 1060 AN XY: 74426

African (AFR) AF: 0.0505 AC: 2097 AN: 41524

American (AMR) AF: 0.00654 AC: 100 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68004

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00594 Hom.: 42

Bravo AF: 0.0171

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0472 AC: 208

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00477 AC: 579

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.090
Sift	Benign	0.036	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.95	P
Vest4		0.41
MVP		0.14
MPC		0.54
ClinPred		0.031	T
GERP RS		-2.2
PromoterAI		-0.0090	Neutral
Varity_R		0.17
gMVP		0.39
Mutation Taster		=100/0	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: rs75762018; hg19: chr1-207071206;