Genetic Variant IL15RA:p.Ala325Ser (chr10-5943662-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000620345.4(IL15RA):c.973G>T(p.Ala325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,226 control chromosomes in the GnomAD database, including 6,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6556 hom., cov: 32)

Exomes 𝑓: 0.20 ( 2 hom. )

Consequence

IL15RA
ENST00000620345.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0590

Publications

5 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:

ENSG00000232807 (HGNC:):

ENSG00000232807 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 (MetaRNN=0.004617363).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105376384	NR_188178.1 link	n.514G>T	non_coding_transcript_exon_variant	Exon 2 of 2
LOC105376384	NR_188179.1 link	n.388G>T	non_coding_transcript_exon_variant	Exon 2 of 2
LOC105376384	NR_188180.1 link	n.260+1993G>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
IL15RA	ENST00000620345.4 link	c.973G>T	p.Ala325Ser	missense_variant	Exon 8 of 8	1	ENSP00000479839.1	K9N163
ENSG00000232807	ENST00000448685.1 link	n.338G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
ENSG00000232807	ENST00000454321.1 link	n.223G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41181

AN:

152014

Hom.:

6554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.202

AC:

AN:

Hom.:

Cov.:

AF XY:

0.185

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.135

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

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:

0.271

AC:

41208

AN:

152132

Hom.:

6556

Cov.:

AF XY:

0.285

AC XY:

21162

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.296

AC:

12292

AN:

41496

American (AMR)

AF:

0.411

AC:

6279

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1029

AN:

3470

East Asian (EAS)

AF:

0.619

AC:

3193

AN:

5160

South Asian (SAS)

AF:

0.503

AC:

2426

AN:

4826

European-Finnish (FIN)

AF:

0.236

AC:

2499

AN:

10594

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12677

AN:

67980

Other (OTH)

AF:

0.282

AC:

595

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1438

2876

4315

5753

7191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.225

Hom.:

1555

Bravo

AF:

0.285

TwinsUK

AF:

0.184

AC:

681

ALSPAC

AF:

0.189

AC:

727

Asia WGS

AF:

0.498

AC:

1731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.5

(source)

DANN

Benign

0.72

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0046

PhyloP100

-0.059

Vest4

0.075

MVP

0.23

GERP RS

-0.87

Splicing

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