Genetic Variant IL15:c.*517G>T (chr4-141733365-G-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_000585.5(IL15):c.*517G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,506 control chromosomes in the GnomAD database, including 335 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 0.065 ( 335 hom., cov: 33)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

IL15
NM_000585.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

Publications

6 publications found

Variant links:

Genes affected

IL15 (HGNC:5977): (interleukin 15) The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]

IL15 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000585.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL15	NM_000585.5	MANE Select	c.*517G>T	3_prime_UTR	Exon 8 of 8	NP_000576.1
IL15	NR_037840.3		n.1869G>T	non_coding_transcript_exon	Exon 8 of 8
IL15	NM_172175.3		c.*517G>T	3_prime_UTR	Exon 10 of 10	NP_751915.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL15	ENST00000320650.9	TSL:1 MANE Select	c.*517G>T	3_prime_UTR	Exon 8 of 8	ENSP00000323505.4
IL15	ENST00000296545.11	TSL:1	c.*517G>T	3_prime_UTR	Exon 8 of 8	ENSP00000296545.7
IL15	ENST00000394159.2	TSL:1	c.*517G>T	3_prime_UTR	Exon 5 of 5	ENSP00000377714.1

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9896

AN:

152132

Hom.:

335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0480

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0918

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0683

Gnomad OTH

AF:

0.0770

GnomAD4 exome

AF:

0.0433

AC:

AN:

254

Hom.:

Cov.:

AF XY:

0.0389

AC XY:

AN XY:

180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.143

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0374

AC:

AN:

214

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0651

AC:

9909

AN:

152252

Hom.:

335

Cov.:

AF XY:

0.0639

AC XY:

4755

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0770

AC:

3198

AN:

41536

American (AMR)

AF:

0.0479

AC:

733

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0919

AC:

443

AN:

4822

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10606

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0683

AC:

4647

AN:

68020

Other (OTH)

AF:

0.0762

AC:

161

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

493

987

1480

1974

2467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0679

Hom.:

188

Bravo

AF:

0.0651

Asia WGS

AF:

0.0420

AC:

145

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.96

(source)

DANN

Benign

0.52

PhyloP100

-0.13

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