Variant 10-5966190-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002189.4(IL15RA):c.238G>T(p.Ala80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,052 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.152

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:

LOC107984200 (HGNC:):

LOC107984200 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050658673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15RA	NM_002189.4 linkuse as main transcript	c.238G>T	p.Ala80Ser	missense_variant	2/7	ENST00000379977.8	NP_002180.1
LOC107984200	XR_001747348.2 linkuse as main transcript	n.1458+1869C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8 linkuse as main transcript	c.238G>T	p.Ala80Ser	missense_variant	2/7	1	NM_002189.4	ENSP00000369312	A2	Q13261-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726626

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.238G>T (p.A80S) alteration is located in exon 2 (coding exon 2) of the IL15RA gene. This alteration results from a G to T substitution at nucleotide position 238, causing the alanine (A) at amino acid position 80 to be replaced by a serine (S). 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

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

DANN

Benign

0.86

DEOGEN2

Benign

0.0055

.;T;T;.;.;.;T;.;.;T;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.64

T;T;T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.051

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N;.;.;N;.;N;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.15

.;.;N;.;.;N;N;N;N;.;.;N;N

REVEL

Benign

0.0030

Sift

Benign

0.66

.;.;T;.;.;T;T;T;T;.;.;T;T

Sift4G

Benign

0.79

T;T;T;T;T;T;T;T;T;T;T;.;T

Polyphen

0.025

.;.;B;.;.;B;.;.;.;.;.;.;.

Vest4

0.16

MutPred

0.26

.;.;Gain of glycosylation at A80 (P = 0.0318);.;.;Gain of glycosylation at A80 (P = 0.0318);.;Gain of glycosylation at A80 (P = 0.0318);Gain of glycosylation at A80 (P = 0.0318);.;.;Gain of glycosylation at A80 (P = 0.0318);.;

MVP

0.33

MPC

0.50

ClinPred

0.050

GERP RS

-2.5

Varity_R

0.081

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over