rs10519612

Positions:

• chr4-141732548-A-C
• chr4-141732548-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000585.5(IL15):​c.379-190A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,216 control chromosomes in the GnomAD database, including 1,550 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 (1550 hom., cov: 33)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.379-190A>C		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.298-190A>C		intron_variant			NP_751915.1
IL15	NR_037840.3	n.1242-190A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.379-190A>C		intron_variant		1	NM_000585.5	ENSP00000323505	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16788 AN: 152098 Hom.: 1547 Cov.: 33

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.110 AC: 16802 AN: 152216 Hom.: 1550 Cov.: 33 AF XY: 0.117 AC XY: 8692 AN XY: 74442

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.117

Alfa AF: 0.118 Hom.: 1330

Bravo AF: 0.122

Asia WGS AF: 0.219 AC: 764 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	3.2
DANN	Benign	0.75

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: rs10519612; hg19: chr4-142653701;