rs9282743

Positions:

• chr4-141733365-G-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IL15	NM_000585.5	c.*517G>T		3_prime_UTR_variant	8/8	ENST00000320650.9
IL15	NM_172175.3	c.*517G>T		3_prime_UTR_variant	10/10
IL15	NR_037840.3	n.1869G>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15	ENST00000320650.9	c.*517G>T		3_prime_UTR_variant	8/8	1	NM_000585.5	P1
IL15	ENST00000296545.11	c.*517G>T		3_prime_UTR_variant	8/8	1		P1
IL15	ENST00000394159.2	c.*517G>T		3_prime_UTR_variant	5/5	1
IL15	ENST00000477265.5	c.*517G>T		3_prime_UTR_variant	7/7	1

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

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0680 Hom.: 64

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

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;