Genetic Variant NM_002189.4:c.616+21G>A (chr10-5959733-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002189.4(IL15RA):c.616+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,608,780 control chromosomes in the GnomAD database, including 204,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 22175 hom., cov: 32)

Exomes 𝑓: 0.50 ( 182302 hom. )

Consequence

IL15RA
NM_002189.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

26 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

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15RA	NM_002189.4 link	c.616+21G>A		intron_variant	Intron 5 of 6	ENST00000379977.8	NP_002180.1	Q13261-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8 link	c.616+21G>A		intron_variant	Intron 5 of 6	1	NM_002189.4	ENSP00000369312.3		Q13261-1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80731

AN:

151904

Hom.:

22143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.503

AC:

125429

AN:

249390

AF XY:

0.501

show subpopulations

Gnomad AFR exome

AF:

0.665

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.481

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.498

AC:

725073

AN:

1456756

Hom.:

182302

Cov.:

AF XY:

0.499

AC XY:

361360

AN XY:

724844

show subpopulations

African (AFR)

AF:

0.662

AC:

22112

AN:

33380

American (AMR)

AF:

0.524

AC:

23380

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

13832

AN:

26100

East Asian (EAS)

AF:

0.427

AC:

16938

AN:

39650

South Asian (SAS)

AF:

0.564

AC:

48537

AN:

86112

European-Finnish (FIN)

AF:

0.454

AC:

24036

AN:

52900

Middle Eastern (MID)

AF:

0.513

AC:

2955

AN:

5760

European-Non Finnish (NFE)

AF:

0.490

AC:

542941

AN:

1107998

Other (OTH)

AF:

0.504

AC:

30342

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

17690

35380

53069

70759

88449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16072

32144

48216

64288

80360

<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:

0.532

AC:

80822

AN:

152024

Hom.:

22175

Cov.:

AF XY:

0.529

AC XY:

39285

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.654

AC:

27124

AN:

41482

American (AMR)

AF:

0.510

AC:

7792

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1856

AN:

3468

East Asian (EAS)

AF:

0.424

AC:

2187

AN:

5154

South Asian (SAS)

AF:

0.550

AC:

2651

AN:

4820

European-Finnish (FIN)

AF:

0.433

AC:

4575

AN:

10554

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.485

AC:

32943

AN:

67948

Other (OTH)

AF:

0.510

AC:

1079

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1911

3822

5733

7644

9555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.497

Hom.:

83312

Bravo

AF:

0.541

Asia WGS

AF:

0.496

AC:

1727

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.68

(source)

DANN

Benign

0.64

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over