rs9282743

Variant names:

• chr4-141733365-G-T
• rs9282743
• NM_000585.5:c.*517G>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.*517G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,506 control chromosomes in the GnomAD database, including 335 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 0.065 (335 hom., cov: 33)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: IL15 NM_000585.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.*517G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.*517G>T		3_prime_UTR_variant	Exon 10 of 10		NP_751915.1
IL15	NR_037840.3	n.1869G>T		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.*517G>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9896 AN: 152132 Hom.: 335 Cov.: 33

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.0770

GnomAD4 exome AF: 0.0433 AC: 11 AN: 254 Hom.: 0 Cov.: 0 AF XY: 0.0389 AC XY: 7 AN XY: 180

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 2

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 2

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 10

Gnomad4 SAS exome AF: 0.143 AC: 2 AN: 14

Gnomad4 FIN exome AF: 0.167 AC: 1 AN: 6

Gnomad4 NFE exome AF: 0.0374 AC: 8 AN: 214

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0651 AC: 9909 AN: 152252 Hom.: 335 Cov.: 33 AF XY: 0.0639 AC XY: 4755 AN XY: 74442

Gnomad4 AFR AF: 0.0770 AC: 0.0769935 AN: 0.0769935

Gnomad4 AMR AF: 0.0479 AC: 0.0479336 AN: 0.0479336

Gnomad4 ASJ AF: 0.0933 AC: 0.093318 AN: 0.093318

Gnomad4 EAS AF: 0.00135 AC: 0.00134979 AN: 0.00134979

Gnomad4 SAS AF: 0.0919 AC: 0.0918706 AN: 0.0918706

Gnomad4 FIN AF: 0.0328 AC: 0.0328116 AN: 0.0328116

Gnomad4 NFE AF: 0.0683 AC: 0.0683181 AN: 0.0683181

Gnomad4 OTH AF: 0.0762 AC: 0.0762311 AN: 0.0762311

Alfa AF: 0.0679 Hom.: 188

Bravo AF: 0.0651

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.52
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

Publications

LitVar

Other links and lift over

dbSNP: rs9282743; hg19: chr4-142654518;