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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

26 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL15RANM_002189.4 linkc.616+21G>A intron_variant Intron 5 of 6 ENST00000379977.8 NP_002180.1 Q13261-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL15RAENST00000379977.8 linkc.616+21G>A intron_variant Intron 5 of 6 1 NM_002189.4 ENSP00000369312.3 Q13261-1

Frequencies

GnomAD3 genomes
AF:
0.531
AC:
80731
AN:
151904
Hom.:
22143
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.456
Heterozygous variant carriers
0
17690
35380
53069
70759
88449
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
16072
32144
48216
64288
80360
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.532
AC:
80822
AN:
152024
Hom.:
22175
Cov.:
32
AF XY:
0.529
AC XY:
39285
AN XY:
74294
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1911
3822
5733
7644
9555
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
696
1392
2088
2784
3480
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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 v4.3

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

Publications

Other links and lift over

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