NM_002189.4:c.616+21G>A

Variant names:

• chr10-5959733-C-T
• rs3136618
• NM_002189.4:c.616+21G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	NM_002189.4	MANE Select	c.616+21G>A		intron	N/A	NP_002180.1	Q13261-1
	IL15RA	NM_001256765.1		c.874+21G>A		intron	N/A	NP_001243694.1	G8CVM3
	IL15RA	NM_001351095.2		c.691+21G>A		intron	N/A	NP_001338024.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.616+21G>A		intron	N/A	ENSP00000369312.3	Q13261-1
	IL15RA	ENST00000397248.6	TSL:1	c.874+21G>A		intron	N/A	ENSP00000380421.3	A0A0A0MS77
	IL15RA	ENST00000622442.4	TSL:1	c.769+21G>A		intron	N/A	ENSP00000480949.1	K9N2Q6

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

GnomAD2 exomes AF: 0.503 AC: 125429 AN: 249390 AF XY: 0.501

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 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

African (AFR) AF: 0.662 AC: 22112 AN: 33380

American (AMR) AF: 0.524 AC: 23380 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 13832 AN: 26100

East Asian (EAS) AF: 0.427 AC: 16938 AN: 39650

South Asian (SAS) AF: 0.564 AC: 48537 AN: 86112

European-Finnish (FIN) AF: 0.454 AC: 24036 AN: 52900

Middle Eastern (MID) AF: 0.513 AC: 2955 AN: 5760

European-Non Finnish (NFE) AF: 0.490 AC: 542941 AN: 1107998

Other (OTH) AF: 0.504 AC: 30342 AN: 60216

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

African (AFR) AF: 0.654 AC: 27124 AN: 41482

American (AMR) AF: 0.510 AC: 7792 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2187 AN: 5154

South Asian (SAS) AF: 0.550 AC: 2651 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4575 AN: 10554

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32943 AN: 67948

Other (OTH) AF: 0.510 AC: 1079 AN: 2114

Alfa AF: 0.497 Hom.: 83312

Bravo AF: 0.541

Asia WGS AF: 0.496 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.64
PhyloP100		-1.5
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: rs3136618; hg19: chr10-6001696; COSMIC: COSV66092602; COSMIC: COSV66092602;