rs141171117

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_StrongBP6_Strong

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 cumulative frequency of 0.000795 (AC=1,284) in the gnomAD database across 1,614,152 control chromosomes, including 8 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0107. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely 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

Publications

3 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002189.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BS2

≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 8.; Very high cumulative gnomAD AC = 1284 (any gene).

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL15RA	NM_002189.4	MANE Select	c.715G>A	p.Val239Ile	missense	Exon 7 of 7	NP_002180.1	Q13261-1
IL15RA	NM_001256765.1		c.973G>A	p.Val325Ile	missense	Exon 8 of 8	NP_001243694.1	Q13261
IL15RA	NM_172200.3		c.616G>A	p.Val206Ile	missense	Exon 6 of 6	NP_751950.2	Q13261-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.715G>A	p.Val239Ile	missense	Exon 7 of 7	ENSP00000369312.3	Q13261-1
IL15RA	ENST00000397248.6	TSL:1	c.973G>A	p.Val325Ile	missense	Exon 8 of 8	ENSP00000380421.3	A0A0A0MS77
IL15RA	ENST00000525219.6	TSL:1	c.607G>A	p.Val203Ile	missense	Exon 7 of 7	ENSP00000431529.2	Q13261-10

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

GnomAD2 exomes

AF:

0.00122

AC:

304

AN:

249130

AF XY:

0.000845

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 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

African (AFR)

AF:

0.0111

AC:

372

AN:

33476

American (AMR)

AF:

0.00105

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000205

AC:

228

AN:

1111942

Other (OTH)

AF:

0.000960

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00359

AC:

547

AN:

152340

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

244

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0115

AC:

479

AN:

41582

American (AMR)

AF:

0.00248

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68038

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00143

Hom.:

Bravo

AF:

0.00409

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.000367

AC:

AN:

122576

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.000335

AC:

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.00342

AC:

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.67

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.12

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.61

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.37

REVEL

Benign

0.015

Sift

Benign

0.41

Sift4G

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.011

gMVP

0.067

Mutation Taster

=99/1

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over