Genetic Variant IL15RA:p.Ser121Gly (chr10-5963764-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002189.4(IL15RA):c.361A>G(p.Ser121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,521,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

IL15RA
NM_002189.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Publications

2 publications found

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:

ENSG00000300557 (HGNC:):

ENSG00000300557 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.069499105).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL15RA	NM_002189.4	MANE Select	c.361A>G	p.Ser121Gly	missense	Exon 3 of 7	NP_002180.1	Q13261-1
IL15RA	NM_001256765.1		c.619A>G	p.Ser207Gly	missense	Exon 4 of 8	NP_001243694.1	G8CVM3
IL15RA	NM_001243539.2		c.253A>G	p.Ser85Gly	missense	Exon 3 of 7	NP_001230468.1	Q13261-10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.361A>G	p.Ser121Gly	missense	Exon 3 of 7	ENSP00000369312.3	Q13261-1
IL15RA	ENST00000397248.6	TSL:1	c.619A>G	p.Ser207Gly	missense	Exon 4 of 8	ENSP00000380421.3	A0A0A0MS77
IL15RA	ENST00000622442.4	TSL:1	c.514A>G	p.Ser172Gly	missense	Exon 4 of 8	ENSP00000480949.1	K9N2Q6

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000644

AC:

AN:

170740

AF XY:

0.0000528

show subpopulations

Gnomad AFR exome

AF:

0.000903

Gnomad AMR exome

AF:

0.0000750

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1369872

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

679228

show subpopulations

African (AFR)

AF:

0.000370

AC:

AN:

27052

American (AMR)

AF:

0.0000451

AC:

AN:

22152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23112

East Asian (EAS)

AF:

0.00

AC:

AN:

33132

South Asian (SAS)

AF:

0.00

AC:

AN:

70246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079340

Other (OTH)

AF:

0.000141

AC:

AN:

56548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.000459

AC:

AN:

41416

American (AMR)

AF:

0.000721

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.027

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

1.3

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

REVEL

Benign

0.095

Sift

Benign

0.12

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.21

MVP

0.67

MPC

0.46

ClinPred

0.12

GERP RS

3.5

PromoterAI

0.017

Neutral

(source)

Varity_R

0.065

gMVP

0.35

Mutation Taster

=63/37

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over