dbSNP rs6850492: IL15:c.-3513A>G (chr4-141716152-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000477265.5(IL15):c.-3513A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,354 control chromosomes in the GnomAD database, including 32,249 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 0.64 ( 32160 hom., cov: 32)

Exomes 𝑓: 0.88 ( 89 hom. )

Consequence

IL15
ENST00000477265.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.417

Publications

13 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5 link	c.-99-3214A>G	intron_variant	Intron 2 of 7	ENST00000320650.9	NP_000576.1	P40933-1
IL15	NM_172175.3 link	c.-287-3226A>G	intron_variant	Intron 3 of 9		NP_751915.1	P40933-2
IL15	NR_037840.3 link	n.765-3214A>G	intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9 link	c.-99-3214A>G		intron_variant	Intron 2 of 7	1	NM_000585.5	ENSP00000323505.4		P40933-1

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

98012

AN:

152012

Hom.:

32138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.686

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.625

GnomAD4 exome

AF:

0.883

AC:

196

AN:

222

Hom.:

Cov.:

AF XY:

0.861

AC XY:

105

AN XY:

122

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.966

AC:

168

AN:

174

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.568

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.645

AC:

98082

AN:

152132

Hom.:

32160

Cov.:

AF XY:

0.654

AC XY:

48662

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.685

AC:

28454

AN:

41518

American (AMR)

AF:

0.716

AC:

10945

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.651

AC:

2259

AN:

3472

East Asian (EAS)

AF:

0.945

AC:

4869

AN:

5154

South Asian (SAS)

AF:

0.713

AC:

3437

AN:

4818

European-Finnish (FIN)

AF:

0.678

AC:

7188

AN:

10594

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.572

AC:

38886

AN:

67972

Other (OTH)

AF:

0.629

AC:

1327

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1761

3522

5282

7043

8804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.597

Hom.:

106672

Bravo

AF:

0.649

Asia WGS

AF:

0.803

AC:

2791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.20

(source)

DANN

Benign

0.58

PhyloP100

-0.42

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