chr10-5960507-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002189.4(IL15RA):​c.443C>T​(p.Pro148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15576074).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL15RANM_002189.4 linkuse as main transcriptc.443C>T p.Pro148Leu missense_variant 4/7 ENST00000379977.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL15RAENST00000379977.8 linkuse as main transcriptc.443C>T p.Pro148Leu missense_variant 4/71 NM_002189.4 A2Q13261-1

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000456
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000282
AC:
71
AN:
251464
Hom.:
0
AF XY:
0.000331
AC XY:
45
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000589
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000286
AC:
418
AN:
1461862
Hom.:
1
Cov.:
34
AF XY:
0.000304
AC XY:
221
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000367
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.000295
AC XY:
22
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000903
Hom.:
43
Bravo
AF:
0.000283
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000288
AC:
35
EpiCase
AF:
0.000763
EpiControl
AF:
0.000948

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 GeneticsAug 20, 2023The c.443C>T (p.P148L) alteration is located in exon 4 (coding exon 4) of the IL15RA gene. This alteration results from a C to T substitution at nucleotide position 443, causing the proline (P) at amino acid position 148 to be replaced by a leucine (L). 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
0.093
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.090
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
.;T;D;.;.;.;.;.;T;.;.;T;.;T;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.82
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.16
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.4
.;.;M;.;.;.;.;.;.;.;M;.;.;.;.
MutationTaster
Benign
0.93
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-5.1
.;.;D;.;.;D;D;D;.;D;D;.;.;D;D
REVEL
Benign
0.14
Sift
Uncertain
0.0050
.;.;D;.;.;D;D;D;.;D;D;.;.;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D;D;D;D;D;D;D;.;D
Polyphen
1.0
.;.;D;.;.;D;.;.;.;.;.;.;.;.;.
Vest4
0.26
MVP
0.72
MPC
0.53
ClinPred
0.59
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.069
gMVP
0.25

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: rs201871586; hg19: chr10-6002470; COSMIC: COSV101181694; API