chr10-5963793-G-A

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

Scores

2
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.128
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 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
IL15RANM_002189.4 linkuse as main transcriptc.332C>T p.Thr111Met missense_variant 3/7 ENST00000379977.8
LOC107984200XR_001747348.2 linkuse as main transcriptn.1321-391G>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.332C>T p.Thr111Met missense_variant 3/71 NM_002189.4 A2Q13261-1

Frequencies

GnomAD3 genomes
AF:
0.00371
AC:
565
AN:
152158
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00138
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0214
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00528
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00394
AC:
708
AN:
179836
Hom.:
6
AF XY:
0.00353
AC XY:
351
AN XY:
99426
show subpopulations
Gnomad AFR exome
AF:
0.00146
Gnomad AMR exome
AF:
0.000380
Gnomad ASJ exome
AF:
0.000271
Gnomad EAS exome
AF:
0.0223
Gnomad SAS exome
AF:
0.00101
Gnomad FIN exome
AF:
0.000494
Gnomad NFE exome
AF:
0.00452
Gnomad OTH exome
AF:
0.00254
GnomAD4 exome
AF:
0.00561
AC:
7762
AN:
1383468
Hom.:
40
Cov.:
31
AF XY:
0.00543
AC XY:
3729
AN XY:
686700
show subpopulations
Gnomad4 AFR exome
AF:
0.00100
Gnomad4 AMR exome
AF:
0.000637
Gnomad4 ASJ exome
AF:
0.000508
Gnomad4 EAS exome
AF:
0.0210
Gnomad4 SAS exome
AF:
0.00107
Gnomad4 FIN exome
AF:
0.000605
Gnomad4 NFE exome
AF:
0.00613
Gnomad4 OTH exome
AF:
0.00399
GnomAD4 genome
AF:
0.00371
AC:
565
AN:
152276
Hom.:
3
Cov.:
32
AF XY:
0.00357
AC XY:
266
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00137
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.0215
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00528
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00471
Hom.:
3
Bravo
AF:
0.00420
TwinsUK
AF:
0.00512
AC:
19
ALSPAC
AF:
0.00545
AC:
21
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00465
AC:
40
ExAC
AF:
0.00392
AC:
476
Asia WGS
AF:
0.00722
AC:
25
AN:
3478

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.012
.;T;T;.;.;.;T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.71
T;T;T;T;T;T;T;T;T
MetaRNN
Benign
0.0035
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
.;.;L;.;.;L;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.64
.;.;N;N;.;N;.;.;N
REVEL
Benign
0.031
Sift
Benign
0.075
.;.;T;D;.;T;.;.;T
Sift4G
Uncertain
0.016
D;D;T;D;D;D;D;D;T
Polyphen
0.13
.;.;B;.;.;.;.;.;.
Vest4
0.18
MVP
0.13
MPC
0.54
ClinPred
0.011
T
GERP RS
-2.3
Varity_R
0.015
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.21
Position offset: 48

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: rs41294171; hg19: chr10-6005756; COSMIC: COSV66093013; COSMIC: COSV66093013; API