rs2296135

Positions:

• chr10-5952731-A-C

Variant summary

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

The NM_002189.4(IL15RA):​c.*364T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 265,304 control chromosomes in the GnomAD database, including 42,050 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 0.57 (26213 hom., cov: 33)
  • Exomes 𝑓: 0.52 (15837 hom.)
• Consequence: IL15RA NM_002189.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

IL15RA (HGNC:5978): (interleukin 15 receptor subunit alpha) This gene encodes a cytokine receptor that specifically binds interleukin 15 (IL15) with high affinity. The receptors of IL15 and IL2 share two subunits, IL2R beta and IL2R gamma. This forms the basis of many overlapping biological activities of IL15 and IL2. The protein encoded by this gene is structurally related to IL2R alpha, an additional IL2-specific alpha subunit necessary for high affinity IL2 binding. Unlike IL2RA, IL15RA is capable of binding IL15 with high affinity independent of other subunits, which suggests distinct roles between IL15 and IL2. This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.*364T>G		3_prime_UTR_variant	7/7	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.*364T>G		3_prime_UTR_variant	7/7	1	NM_002189.4	ENSP00000369312	A2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87247 AN: 151992 Hom.: 26174 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.520 AC: 58812 AN: 113194 Hom.: 15837 Cov.: 0 AF XY: 0.522 AC XY: 30358 AN XY: 58180

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.574 AC: 87341 AN: 152110 Hom.: 26213 Cov.: 33 AF XY: 0.568 AC XY: 42185 AN XY: 74334

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.555

Alfa AF: 0.529 Hom.: 37734

Bravo AF: 0.584

Asia WGS AF: 0.515 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2296135; hg19: chr10-5994694;