1-206897861-T-C

Position:

• chr1-206897861-T-C

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL24	NM_006850.3	c.29T>C	p.Leu10Pro	missense_variant	2/7	ENST00000294984.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL24	ENST00000294984.7	c.29T>C	p.Leu10Pro	missense_variant	2/7	1	NM_006850.3	P4

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

GnomAD3 exomes AF: 0.00401 AC: 960 AN: 239354 Hom.: 21 AF XY: 0.00292 AC XY: 377 AN XY: 128998

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 SAS exome AF: 0.0000699

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

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.00395

Gnomad4 ASJ exome AF: 0.00215

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000945

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.00408

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

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00316 Hom.: 18

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
MetaRNN	Benign	0.0023	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.12	N;.;N;N;D
REVEL	Benign	0.090
Sift	Benign	0.036	D;.;D;D;.
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.95	.;.;P;.;.
Vest4		0.41
MVP		0.14
MPC		0.54
ClinPred		0.031	T
GERP RS		-2.2
Varity_R		0.17
gMVP		0.39

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: rs75762018; hg19: chr1-207071206;