Variant 10-5953184-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002189.4(IL15RA):c.715G>A(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,614,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 3 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.613

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]

IL15RA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037511885).

BP6

Variant 10-5953184-C-T is Benign according to our data. Variant chr10-5953184-C-T is described in ClinVar as [Benign]. Clinvar id is 709069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL15RA	NM_002189.4 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	7/7	ENST00000379977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15RA	ENST00000379977.8 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	7/7	1	NM_002189.4	A2	Q13261-1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

547

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00122

AC:

304

AN:

249130

Hom.:

AF XY:

0.000845

AC XY:

114

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000242

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000504

AC:

737

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

306

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152340

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

244

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000784

Hom.:

Bravo

AF:

0.00409

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.67

DANN

Benign

0.59

DEOGEN2

Benign

0.12

T;.;.;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.57

T;T;T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.37

N;.;.;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.41

T;.;.;T;T;D

Sift4G

Benign

0.48

T;T;T;T;T;T

Polyphen

0.010

B;.;.;B;.;.

Vest4

0.031

MVP

0.12

MPC

0.084

ClinPred

0.000069

GERP RS

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.011

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over