rs115008149

Variant names:

• chr1-206900364-A-G
• rs115008149
• NM_006850.3:c.303+7A>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.303+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,613,740 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts 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 0.012 (45 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (39 hom.)
• Consequence: IL24 NM_006850.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002827
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.400
• Publications: 1 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 (BayesDel_noAF=-0.84).
• BP6: Variant 1-206900364-A-G is Benign according to our data. Variant chr1-206900364-A-G is described in ClinVar as Benign. ClinVar VariationId is 715555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1891/152258) while in subpopulation AFR AF = 0.0407 (1692/41538). AF 95% confidence interval is 0.0391. There are 45 homozygotes in GnomAd4. There are 893 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 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.303+7A>G		splice_region intron	N/A	NP_006841.1	Q13007-1
	IL24	NM_001185156.1		c.306+7A>G		splice_region intron	N/A	NP_001172085.1	Q13007-2
	IL24	NM_001185157.1		c.306+7A>G		splice_region 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.303+7A>G		splice_region intron	N/A	ENSP00000294984.2	Q13007-1
	IL24	ENST00000391929.7	TSL:1	c.306+7A>G		splice_region intron	N/A	ENSP00000375795.3	Q13007-2
	IL24	ENST00000367093.3	TSL:1	c.306+7A>G		splice_region intron	N/A	ENSP00000356060.3	Q13007-3

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1878 AN: 152140 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00409 AC: 1029 AN: 251442 AF XY: 0.00313

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.0262

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00178 AC: 2607 AN: 1461482 Hom.: 39 Cov.: 30 AF XY: 0.00165 AC XY: 1199 AN XY: 727062

African (AFR) AF: 0.0404 AC: 1353 AN: 33466

American (AMR) AF: 0.00244 AC: 109 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 616 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000183 AC: 203 AN: 1111654

Other (OTH) AF: 0.00502 AC: 303 AN: 60386

GnomAD4 genome AF: 0.0124 AC: 1891 AN: 152258 Hom.: 45 Cov.: 31 AF XY: 0.0120 AC XY: 893 AN XY: 74436

African (AFR) AF: 0.0407 AC: 1692 AN: 41538

American (AMR) AF: 0.00608 AC: 93 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00677 Hom.: 10

Bravo AF: 0.0137

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000711

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.010		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: rs115008149; hg19: chr1-207073709;