10-5963811-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002189.4(IL15RA):​c.314C>T​(p.Ala105Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.345
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05140099).
BP6
Variant 10-5963811-G-A is Benign according to our data. Variant chr10-5963811-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3285736.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL15RANM_002189.4 linkuse as main transcriptc.314C>T p.Ala105Val missense_variant 3/7 ENST00000379977.8
LOC107984200XR_001747348.2 linkuse as main transcriptn.1321-373G>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.314C>T p.Ala105Val missense_variant 3/71 NM_002189.4 A2Q13261-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000215
AC:
3
AN:
1395196
Hom.:
0
Cov.:
31
AF XY:
0.00000144
AC XY:
1
AN XY:
692788
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000135
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 18, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
9.2
DANN
Benign
0.86
DEOGEN2
Benign
0.0018
.;T;T;.;.;.;T;.;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.63
T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.051
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.90
.;.;N;.;.;N;.;.;.
MutationTaster
Benign
0.92
D;D;D;D;N;N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.20
.;.;N;.;.;N;.;.;N
REVEL
Benign
0.035
Sift
Benign
0.65
.;.;T;.;.;T;.;.;T
Sift4G
Benign
0.54
T;T;T;T;T;T;T;T;T
Polyphen
0.017
.;.;B;.;.;.;.;.;.
Vest4
0.14
MVP
0.34
MPC
0.51
ClinPred
0.019
T
GERP RS
-1.7
Varity_R
0.077
gMVP
0.096

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs143835821; hg19: chr10-6005774; COSMIC: COSV66093361; COSMIC: COSV66093361; API