chr10-5959733-C-T

Position:

• chr10-5959733-C-T

Variant summary

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

The NM_002189.4(IL15RA):​c.616+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,608,780 control chromosomes in the GnomAD database, including 204,477 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 0.53 (22175 hom., cov: 32)
  • Exomes 𝑓: 0.50 (182302 hom.)
• Consequence: IL15RA NM_002189.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL15RA	NM_002189.4	c.616+21G>A		intron_variant		ENST00000379977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15RA	ENST00000379977.8	c.616+21G>A		intron_variant		1	NM_002189.4	A2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80731 AN: 151904 Hom.: 22143 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.503 AC: 125429 AN: 249390 Hom.: 32106 AF XY: 0.501 AC XY: 67573 AN XY: 134886

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.414

Gnomad SAS exome AF: 0.562

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.498 AC: 725073 AN: 1456756 Hom.: 182302 Cov.: 32 AF XY: 0.499 AC XY: 361360 AN XY: 724844

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.532 AC: 80822 AN: 152024 Hom.: 22175 Cov.: 32 AF XY: 0.529 AC XY: 39285 AN XY: 74294

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.510

Alfa AF: 0.488 Hom.: 40958

Bravo AF: 0.541

Asia WGS AF: 0.496 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.64

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: rs3136618; hg19: chr10-6001696; COSMIC: COSV66092602; COSMIC: COSV66092602;