rs10519613

chr4-141732931-C-A

Variant summary

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

The NM_000585.5(IL15):c.*83C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,512,148 control chromosomes in the GnomAD database, including 13,936 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 (1546 hom., cov: 33)
  • Exomes 𝑓: 0.11 (12390 hom.)
• Consequence: IL15 NM_000585.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.65).
• 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/exons	MANE	UniProt
IL15	NM_000585.5	c.*83C>A		3_prime_UTR_variant	8/8	ENST00000320650.9
IL15	NM_172175.3	c.*83C>A		3_prime_UTR_variant	10/10
IL15	NR_037840.3	n.1435C>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15	ENST00000320650.9	c.*83C>A		3_prime_UTR_variant	8/8	1	NM_000585.5	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16765 AN: 152050 Hom.: 1543 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.114 AC: 154953 AN: 1359980 Hom.: 12390 Cov.: 29 AF XY: 0.114 AC XY: 76329 AN XY: 669248

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.110 AC: 16778 AN: 152168 Hom.: 1546 Cov.: 33 AF XY: 0.117 AC XY: 8674 AN XY: 74384

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.116

Alfa AF: 0.115 Hom.: 2128

Bravo AF: 0.122

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.0
Dann	Benign	0.72

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: rs10519613; hg19: chr4-142654084; COSMIC: COSV56728106; COSMIC: COSV56728106;