chr10-5952731-A-C

Variant names:

• chr10-5952731-A-C
• rs2296135
• ENST00000534292.5:n.1349T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000534292.5(IL15RA):​n.1349T>G variant causes a non coding transcript exon 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 ENST00000534292.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.*364T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.*364T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_002189.4	ENSP00000369312.3

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

African (AFR) AF: 0.752 AC: 2512 AN: 3340

American (AMR) AF: 0.463 AC: 2327 AN: 5024

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1833 AN: 3324

East Asian (EAS) AF: 0.431 AC: 3002 AN: 6964

South Asian (SAS) AF: 0.579 AC: 5668 AN: 9788

European-Finnish (FIN) AF: 0.485 AC: 3042 AN: 6272

Middle Eastern (MID) AF: 0.565 AC: 297 AN: 526

European-Non Finnish (NFE) AF: 0.514 AC: 36621 AN: 71264

Other (OTH) AF: 0.525 AC: 3510 AN: 6692

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

African (AFR) AF: 0.754 AC: 31284 AN: 41512

American (AMR) AF: 0.489 AC: 7468 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1873 AN: 3472

East Asian (EAS) AF: 0.435 AC: 2254 AN: 5176

South Asian (SAS) AF: 0.562 AC: 2712 AN: 4828

European-Finnish (FIN) AF: 0.430 AC: 4541 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35268 AN: 67968

Other (OTH) AF: 0.555 AC: 1173 AN: 2112

Alfa AF: 0.531 Hom.: 49178

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
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

Other links and lift over

dbSNP: rs2296135; hg19: chr10-5994694;