rs12508866

Variant names:

• chr4-141644540-T-C
• rs12508866
• NM_000585.5:c.-222+7792T>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.-222+7792T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,142 control chromosomes in the GnomAD database, including 2,763 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 0.17 (2763 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-222+7792T>C		intron_variant	Intron 1 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-624+7792T>C		intron_variant	Intron 1 of 9		NP_751915.1
IL15	NR_037840.3	n.642+7316T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-222+7792T>C		intron_variant	Intron 1 of 7	1	NM_000585.5	ENSP00000323505.4
IL15	ENST00000296545.11	c.-222+7316T>C		intron_variant	Intron 1 of 7	1		ENSP00000296545.7
IL15	ENST00000529613.5	c.-314+7316T>C		intron_variant	Intron 1 of 7	5		ENSP00000435462.1
IL15	ENST00000514653.5	c.-624+7792T>C		intron_variant	Intron 1 of 9	5		ENSP00000422271.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26279 AN: 152024 Hom.: 2763 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.173 AC: 26288 AN: 152142 Hom.: 2763 Cov.: 32 AF XY: 0.172 AC XY: 12789 AN XY: 74376

African (AFR) AF: 0.0632 AC: 2623 AN: 41528

American (AMR) AF: 0.274 AC: 4182 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3468

East Asian (EAS) AF: 0.131 AC: 678 AN: 5166

South Asian (SAS) AF: 0.180 AC: 868 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10606

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15283 AN: 67980

Other (OTH) AF: 0.170 AC: 358 AN: 2108

Alfa AF: 0.214 Hom.: 2096

Bravo AF: 0.180

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		-0.091
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: rs12508866; hg19: chr4-142565693;