Genetic Variant IL15:c.*546T>C (chr4-141733394-T-C) – 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.*546T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,214 control chromosomes in the GnomAD database, including 42,534 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 0.74 ( 42517 hom., cov: 32)

Exomes 𝑓: 0.68 ( 17 hom. )

Consequence

IL15
NM_000585.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.952

Publications

30 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 (EAS) allele frequency at 95% confidence interval = 0.924 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	UniProt
IL15	NM_000585.5	MANE Select	c.*546T>C	3_prime_UTR	Exon 8 of 8	NP_000576.1	P40933-1
IL15	NM_172175.3		c.*546T>C	3_prime_UTR	Exon 10 of 10	NP_751915.1	P40933-2
IL15	NR_037840.3		n.1898T>C	non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL15	ENST00000320650.9	TSL:1 MANE Select	c.*546T>C	3_prime_UTR	Exon 8 of 8	ENSP00000323505.4	P40933-1
IL15	ENST00000296545.11	TSL:1	c.*546T>C	3_prime_UTR	Exon 8 of 8	ENSP00000296545.7	P40933-1
IL15	ENST00000394159.2	TSL:1	c.*546T>C	3_prime_UTR	Exon 5 of 5	ENSP00000377714.1	P40933-2

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112557

AN:

152020

Hom.:

42462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.772

Gnomad ASJ

AF:

0.751

Gnomad EAS

AF:

0.947

Gnomad SAS

AF:

0.807

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.720

GnomAD4 exome

AF:

0.684

AC:

AN:

Hom.:

Cov.:

AF XY:

0.679

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.656

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.741

AC:

112672

AN:

152138

Hom.:

42517

Cov.:

AF XY:

0.747

AC XY:

55565

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.868

AC:

36033

AN:

41512

American (AMR)

AF:

0.773

AC:

11808

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

2606

AN:

3472

East Asian (EAS)

AF:

0.947

AC:

4909

AN:

5186

South Asian (SAS)

AF:

0.807

AC:

3895

AN:

4828

European-Finnish (FIN)

AF:

0.715

AC:

7542

AN:

10550

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.641

AC:

43582

AN:

67990

Other (OTH)

AF:

0.723

AC:

1529

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1452

2905

4357

5810

7262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.671

Hom.:

24539

Bravo

AF:

0.748

Asia WGS

AF:

0.854

AC:

2970

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

1.0

(source)

DANN

Benign

0.60

PhyloP100

-0.95

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