Genetic Variant IL15RA:c.89-311G>A (chr10-5966650-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.89-311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 151,816 control chromosomes in the GnomAD database, including 55,948 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 0.86 ( 55948 hom., cov: 28)

Consequence

IL15RA
NM_002189.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.927

Publications

8 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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
IL15RA	NM_002189.4	MANE Select	c.89-311G>A	intron	N/A	NP_002180.1	Q13261-1
IL15RA	NM_001256765.1		c.347-311G>A	intron	N/A	NP_001243694.1	G8CVM3
IL15RA	NM_001351095.2		c.263-311G>A	intron	N/A	NP_001338024.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.89-311G>A	intron	N/A	ENSP00000369312.3	Q13261-1
IL15RA	ENST00000397248.6	TSL:1	c.347-311G>A	intron	N/A	ENSP00000380421.3	A0A0A0MS77
IL15RA	ENST00000622442.4	TSL:1	c.242-311G>A	intron	N/A	ENSP00000480949.1	K9N2Q6

Frequencies

GnomAD3 genomes

AF:

0.856

AC:

129854

AN:

151696

Hom.:

55907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.942

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.888

Gnomad OTH

AF:

0.881

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.856

AC:

129957

AN:

151816

Hom.:

55948

Cov.:

AF XY:

0.848

AC XY:

62889

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.862

AC:

35695

AN:

41426

American (AMR)

AF:

0.837

AC:

12763

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

3271

AN:

3472

East Asian (EAS)

AF:

0.660

AC:

3353

AN:

5078

South Asian (SAS)

AF:

0.830

AC:

3963

AN:

4774

European-Finnish (FIN)

AF:

0.715

AC:

7537

AN:

10546

Middle Eastern (MID)

AF:

0.908

AC:

267

AN:

294

European-Non Finnish (NFE)

AF:

0.888

AC:

60345

AN:

67952

Other (OTH)

AF:

0.883

AC:

1859

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

901

1802

2703

3604

4505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.887

Hom.:

95675

Bravo

AF:

0.868

Asia WGS

AF:

0.747

AC:

2586

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.83

(source)

DANN

Benign

0.58

PhyloP100

-0.93

PromoterAI

0.011

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over