4-141678069-C-T

Variant names:

• chr4-141678069-C-T
• rs13117878
• NM_000585.5:c.-100+21762C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000585.5(IL15):​c.-100+21762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,912 control chromosomes in the GnomAD database, including 19,913 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 0.51 (19913 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-100+21762C>T		intron_variant	Intron 2 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-501-10753C>T		intron_variant	Intron 2 of 9		NP_751915.1
IL15	NR_037840.3	n.764+21762C>T		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-100+21762C>T		intron_variant	Intron 2 of 7	1	NM_000585.5	ENSP00000323505.4
IL15	ENST00000296545.11	c.-100+21762C>T		intron_variant	Intron 2 of 7	1		ENSP00000296545.7
IL15	ENST00000529613.5	c.-313-10753C>T		intron_variant	Intron 1 of 7	5		ENSP00000435462.1
IL15	ENST00000514653.5	c.-501-10753C>T		intron_variant	Intron 2 of 9	5		ENSP00000422271.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77122 AN: 151794 Hom.: 19906 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.471

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77159 AN: 151912 Hom.: 19913 Cov.: 32 AF XY: 0.515 AC XY: 38256 AN XY: 74242

African (AFR) AF: 0.482 AC: 19962 AN: 41410

American (AMR) AF: 0.472 AC: 7203 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4369 AN: 5158

South Asian (SAS) AF: 0.631 AC: 3040 AN: 4818

European-Finnish (FIN) AF: 0.585 AC: 6161 AN: 10538

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32828 AN: 67938

Other (OTH) AF: 0.476 AC: 1007 AN: 2114

Alfa AF: 0.503 Hom.: 17133

Bravo AF: 0.496

Asia WGS AF: 0.698 AC: 2427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.33
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13117878; hg19: chr4-142599222;