10-5956696-C-T

Position:

• chr10-5956696-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.617-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 152,272 control chromosomes in the GnomAD database, including 730 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 0.093 (730 hom., cov: 32)
• Consequence: IL15RA NM_002189.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.617-242G>A		intron_variant		ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.617-242G>A		intron_variant		1	NM_002189.4	ENSP00000369312	A2

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14069 AN: 152154 Hom.: 726 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0989

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0926 AC: 14094 AN: 152272 Hom.: 730 Cov.: 32 AF XY: 0.0903 AC XY: 6724 AN XY: 74444

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.0969

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0900 Hom.: 662

Bravo AF: 0.102

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.71

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: rs2296141; hg19: chr10-5998659;