Genetic Variant NM_000585.5:c.*83C>A (chr4-141732931-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 NM_000585.5(IL15):c.*83C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,512,148 control chromosomes in the GnomAD database, including 13,936 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 0.11 ( 1546 hom., cov: 33)

Exomes 𝑓: 0.11 ( 12390 hom. )

Consequence

IL15
NM_000585.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256

Publications

35 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:

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=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5 link	c.*83C>A	3_prime_UTR_variant	Exon 8 of 8	ENST00000320650.9	NP_000576.1	P40933-1
IL15	NR_037840.3 link	n.1435C>A	non_coding_transcript_exon_variant	Exon 8 of 8
IL15	NM_172175.3 link	c.*83C>A	3_prime_UTR_variant	Exon 10 of 10		NP_751915.1	P40933-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9 link	c.*83C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000585.5	ENSP00000323505.4		P40933-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16765

AN:

152050

Hom.:

1543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.114

AC:

154953

AN:

1359980

Hom.:

12390

Cov.:

AF XY:

0.114

AC XY:

76329

AN XY:

669248

show subpopulations

African (AFR)

AF:

0.0241

AC:

704

AN:

29206

American (AMR)

AF:

0.378

AC:

9701

AN:

25632

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2216

AN:

21198

East Asian (EAS)

AF:

0.443

AC:

16276

AN:

36766

South Asian (SAS)

AF:

0.122

AC:

8365

AN:

68788

European-Finnish (FIN)

AF:

0.121

AC:

5993

AN:

49534

Middle Eastern (MID)

AF:

0.153

AC:

810

AN:

5300

European-Non Finnish (NFE)

AF:

0.0974

AC:

104002

AN:

1067676

Other (OTH)

AF:

0.123

AC:

6886

AN:

55880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6716

13431

20147

26862

33578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4124

8248

12372

16496

20620

<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:

0.110

AC:

16778

AN:

152168

Hom.:

1546

Cov.:

AF XY:

0.117

AC XY:

8674

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0287

AC:

1191

AN:

41548

American (AMR)

AF:

0.265

AC:

4052

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

331

AN:

3464

East Asian (EAS)

AF:

0.413

AC:

2131

AN:

5156

South Asian (SAS)

AF:

0.118

AC:

567

AN:

4824

European-Finnish (FIN)

AF:

0.122

AC:

1294

AN:

10578

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6889

AN:

68004

Other (OTH)

AF:

0.116

AC:

246

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

694

1389

2083

2778

3472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.112

Hom.:

3233

Bravo

AF:

0.122

Asia WGS

AF:

0.217

AC:

756

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.0

(source)

DANN

Benign

0.72

PhyloP100

0.26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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