rs10519612

Variant names:

• chr4-141732548-A-C
• rs10519612
• NM_000585.5:c.379-190A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.379-190A>C		intron_variant	Intron 7 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.298-190A>C		intron_variant	Intron 9 of 9		NP_751915.1
IL15	NR_037840.3	n.1242-190A>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.379-190A>C		intron_variant	Intron 7 of 7	1	NM_000585.5	ENSP00000323505.4

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

African (AFR) AF: 0.0287 AC: 1193 AN: 41562

American (AMR) AF: 0.267 AC: 4076 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2131 AN: 5166

South Asian (SAS) AF: 0.117 AC: 563 AN: 4818

European-Finnish (FIN) AF: 0.122 AC: 1298 AN: 10598

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6885 AN: 67998

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.116 Hom.: 1559

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
PhyloP100		0.33
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: rs10519612; hg19: chr4-142653701;