dbSNP rs116501276: IL15:p.Leu117Val (chr4-141729955-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000585.5(IL15):c.349C>G(p.Leu117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,607,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

IL15
NM_000585.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0200

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39628014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5 link	c.349C>G	p.Leu117Val	missense_variant	Exon 7 of 8	ENST00000320650.9	NP_000576.1	P40933-1
IL15	NM_172175.3 link	c.268C>G	p.Leu90Val	missense_variant	Exon 9 of 10		NP_751915.1	P40933-2
IL15	NR_037840.3 link	n.1212C>G		non_coding_transcript_exon_variant	Exon 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9 link	c.349C>G	p.Leu117Val	missense_variant	Exon 7 of 8	1	NM_000585.5	ENSP00000323505.4		P40933-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455806

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;D;.;D;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.71

.;.;.;T;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.40

T;T;T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.3

M;M;.;M;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Benign

0.19

T;T;T;T;T;T

Polyphen

0.98

D;D;.;D;.;.

Vest4

0.19

MutPred

0.74

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);.;.;

MVP

0.37

MPC

0.049

ClinPred

0.49

GERP RS

3.7

Varity_R

0.17

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over