NM_002189.4:c.219G>A

Variant names:

• chr10-5966209-C-T
• rs2296139
• NM_002189.4:c.219G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002189.4(IL15RA):​c.219G>A​(p.Thr73Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,654 control chromosomes in the GnomAD database, including 17,420 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 0.16 (2087 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15333 hom.)
• Consequence: IL15RA NM_002189.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.03
• Publications: 28 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]

ENSG00000300557 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).
• BP7: Synonymous conserved (PhyloP=-4.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.219G>A	p.Thr73Thr	synonymous_variant	Exon 2 of 7	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.219G>A	p.Thr73Thr	synonymous_variant	Exon 2 of 7	1	NM_002189.4	ENSP00000369312.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23996 AN: 151984 Hom.: 2074 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.166 AC: 41777 AN: 251178 AF XY: 0.161

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.138 AC: 201874 AN: 1461552 Hom.: 15333 Cov.: 32 AF XY: 0.138 AC XY: 100455 AN XY: 727042

African (AFR) AF: 0.172 AC: 5748 AN: 33478

American (AMR) AF: 0.258 AC: 11520 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4055 AN: 26130

East Asian (EAS) AF: 0.299 AC: 11879 AN: 39688

South Asian (SAS) AF: 0.143 AC: 12338 AN: 86246

European-Finnish (FIN) AF: 0.112 AC: 5990 AN: 53414

Middle Eastern (MID) AF: 0.165 AC: 953 AN: 5766

European-Non Finnish (NFE) AF: 0.127 AC: 140814 AN: 1111750

Other (OTH) AF: 0.142 AC: 8577 AN: 60386

GnomAD4 genome AF: 0.158 AC: 24044 AN: 152102 Hom.: 2087 Cov.: 32 AF XY: 0.160 AC XY: 11869 AN XY: 74358

African (AFR) AF: 0.170 AC: 7053 AN: 41492

American (AMR) AF: 0.219 AC: 3348 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1567 AN: 5168

South Asian (SAS) AF: 0.140 AC: 676 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1233 AN: 10592

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9137 AN: 67980

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.144 Hom.: 6483

Bravo AF: 0.170

Asia WGS AF: 0.170 AC: 594 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.036
DANN	Benign	0.66
PhyloP100		-4.0
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2296139; hg19: chr10-6008172; COSMIC: COSV66092686; COSMIC: COSV66092686;