Genetic Variant IL15:c.*269A>T (chr4-141733117-A-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.*269A>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 0.0212 in 292,796 control chromosomes in the GnomAD database, including 733 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 0.020 ( 295 hom., cov: 33)

Exomes 𝑓: 0.023 ( 438 hom. )

Consequence

IL15
NM_000585.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.596

Publications

2 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5 link	c.*269A>T	3_prime_UTR_variant	Exon 8 of 8	ENST00000320650.9	NP_000576.1	P40933-1
IL15	NR_037840.3 link	n.1621A>T	non_coding_transcript_exon_variant	Exon 8 of 8
IL15	NM_172175.3 link	c.*269A>T	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.*269A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_000585.5	ENSP00000323505.4		P40933-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2974

AN:

152156

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.0231

AC:

3248

AN:

140522

Hom.:

438

Cov.:

AF XY:

0.0233

AC XY:

1658

AN XY:

71216

show subpopulations

African (AFR)

AF:

0.00175

AC:

AN:

3424

American (AMR)

AF:

0.0631

AC:

176

AN:

2790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4024

East Asian (EAS)

AF:

0.368

AC:

2260

AN:

6134

South Asian (SAS)

AF:

0.0324

AC:

299

AN:

9228

European-Finnish (FIN)

AF:

0.0277

AC:

158

AN:

5714

Middle Eastern (MID)

AF:

0.00166

AC:

AN:

604

European-Non Finnish (NFE)

AF:

0.00188

AC:

189

AN:

100298

Other (OTH)

AF:

0.0191

AC:

159

AN:

8306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

114

227

341

454

568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.0195

AC:

2972

AN:

152274

Hom.:

295

Cov.:

AF XY:

0.0226

AC XY:

1686

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41564

American (AMR)

AF:

0.0408

AC:

624

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.315

AC:

1631

AN:

5172

South Asian (SAS)

AF:

0.0402

AC:

194

AN:

4820

European-Finnish (FIN)

AF:

0.0284

AC:

301

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00213

AC:

145

AN:

68020

Other (OTH)

AF:

0.0142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

129

257

386

514

643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00821

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.130

AC:

454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

(source)

DANN

Benign

0.77

PhyloP100

0.60

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over