chr10-5963793-G-A
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_002189.4(IL15RA):c.332C>T(p.Thr111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,535,744 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0056 ( 40 hom. )
Consequence
IL15RA
NM_002189.4 missense
NM_002189.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.128
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 Benign. Variant got -16 ACMG points.
BP6
Variant 10-5963793-G-A is Benign according to our data. Variant chr10-5963793-G-A is described in ClinVar as [Benign]. Clinvar id is 770960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00371 (565/152276) while in subpopulation EAS AF= 0.0215 (111/5170). AF 95% confidence interval is 0.0182. There are 3 homozygotes in gnomad4. There are 266 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL15RA | NM_002189.4 | c.332C>T | p.Thr111Met | missense_variant | 3/7 | ENST00000379977.8 | |
LOC107984200 | XR_001747348.2 | n.1321-391G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL15RA | ENST00000379977.8 | c.332C>T | p.Thr111Met | missense_variant | 3/7 | 1 | NM_002189.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00371 AC: 565AN: 152158Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00394 AC: 708AN: 179836Hom.: 6 AF XY: 0.00353 AC XY: 351AN XY: 99426
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GnomAD4 exome AF: 0.00561 AC: 7762AN: 1383468Hom.: 40 Cov.: 31 AF XY: 0.00543 AC XY: 3729AN XY: 686700
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GnomAD4 genome AF: 0.00371 AC: 565AN: 152276Hom.: 3 Cov.: 32 AF XY: 0.00357 AC XY: 266AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.;.;L;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;N;.;N;.;.;N
REVEL
Benign
Sift
Benign
.;.;T;D;.;T;.;.;T
Sift4G
Uncertain
D;D;T;D;D;D;D;D;T
Polyphen
0.13
.;.;B;.;.;.;.;.;.
Vest4
MVP
MPC
0.54
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 48
Find out detailed SpliceAI scores and Pangolin per-transcript scores at