rs12498901

Variant names:

• chr4-141681977-G-C
• rs12498901
• NM_000585.5:c.-100+25670G>C

Variant summary

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

The NM_000585.5(IL15):​c.-100+25670G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,168 control chromosomes in the GnomAD database, including 1,007 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 0.11 (1007 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-100+25670G>C		intron_variant	Intron 2 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-501-6845G>C		intron_variant	Intron 2 of 9		NP_751915.1
IL15	NR_037840.3	n.764+25670G>C		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-100+25670G>C		intron_variant	Intron 2 of 7	1	NM_000585.5	ENSP00000323505.4
IL15	ENST00000296545.11	c.-100+25670G>C		intron_variant	Intron 2 of 7	1		ENSP00000296545.7
IL15	ENST00000529613.5	c.-313-6845G>C		intron_variant	Intron 1 of 7	5		ENSP00000435462.1
IL15	ENST00000514653.5	c.-501-6845G>C		intron_variant	Intron 2 of 9	5		ENSP00000422271.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16653 AN: 152050 Hom.: 1007 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.109 AC: 16660 AN: 152168 Hom.: 1007 Cov.: 32 AF XY: 0.105 AC XY: 7794 AN XY: 74396

African (AFR) AF: 0.0864 AC: 3587 AN: 41510

American (AMR) AF: 0.0859 AC: 1313 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3466

East Asian (EAS) AF: 0.0489 AC: 253 AN: 5176

South Asian (SAS) AF: 0.101 AC: 487 AN: 4822

European-Finnish (FIN) AF: 0.0588 AC: 623 AN: 10596

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9638 AN: 67996

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.127 Hom.: 162

Bravo AF: 0.111

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.4
DANN	Benign	0.58
PhyloP100		-0.13
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: rs12498901; hg19: chr4-142603130;