chr10-5963761-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002189.4(IL15RA):​c.364C>T​(p.Leu122Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,520,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.228
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033801585).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL15RANM_002189.4 linkuse as main transcriptc.364C>T p.Leu122Phe missense_variant 3/7 ENST00000379977.8
LOC107984200XR_001747348.2 linkuse as main transcriptn.1321-423G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL15RAENST00000379977.8 linkuse as main transcriptc.364C>T p.Leu122Phe missense_variant 3/71 NM_002189.4 A2Q13261-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000658
AC:
9
AN:
1368384
Hom.:
0
Cov.:
30
AF XY:
0.00000885
AC XY:
6
AN XY:
678308
show subpopulations
Gnomad4 AFR exome
AF:
0.000185
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000708
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 10, 2024The c.364C>T (p.L122F) alteration is located in exon 3 (coding exon 3) of the IL15RA gene. This alteration results from a C to T substitution at nucleotide position 364, causing the leucine (L) at amino acid position 122 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0095
.;T;T;.;.;.;T;.;.
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.62
T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.034
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
.;.;N;.;.;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;N;N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.21
.;.;N;.;.;N;.;.;N
REVEL
Benign
0.011
Sift
Benign
0.19
.;.;T;.;.;T;.;.;T
Sift4G
Benign
0.22
T;T;T;T;T;T;T;T;T
Polyphen
0.0010
.;.;B;.;.;.;.;.;.
Vest4
0.12
MVP
0.30
MPC
0.12
ClinPred
0.022
T
GERP RS
1.5
Varity_R
0.026
gMVP
0.10

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200674526; hg19: chr10-6005724; API