NM_000585.5:c.240+518A>G

Variant names:

• chr4-141728502-A-G
• rs3775597
• NM_000585.5:c.240+518A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000585.5(IL15):​c.240+518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,112 control chromosomes in the GnomAD database, including 1,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1857 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 5 publications found

Genes affected

IL15 (HGNC:5977): (interleukin 15) The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.240+518A>G		intron_variant	Intron 6 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.159+518A>G		intron_variant	Intron 8 of 9		NP_751915.1
IL15	NR_037840.3	n.1103+518A>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.240+518A>G		intron_variant	Intron 6 of 7	1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20594 AN: 151994 Hom.: 1854 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.0903

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20609 AN: 152112 Hom.: 1857 Cov.: 32 AF XY: 0.141 AC XY: 10448 AN XY: 74358

African (AFR) AF: 0.117 AC: 4859 AN: 41524

American (AMR) AF: 0.272 AC: 4151 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0903 AC: 313 AN: 3466

East Asian (EAS) AF: 0.414 AC: 2135 AN: 5160

South Asian (SAS) AF: 0.120 AC: 579 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6886 AN: 67980

Other (OTH) AF: 0.143 AC: 302 AN: 2110

Alfa AF: 0.114 Hom.: 1294

Bravo AF: 0.151

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.094
DANN	Benign	0.65
PhyloP100		-0.62
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: rs3775597; hg19: chr4-142649655;