4-141719309-C-T

Position:

• chr4-141719309-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477265.5(IL15):​c.-356C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 527,180 control chromosomes in the GnomAD database, including 101,208 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 0.62 (29730 hom., cov: 30)
  • Exomes 𝑓: 0.61 (71478 hom.)
• Consequence: IL15 ENST00000477265.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.-99-57C>T		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-287-69C>T		intron_variant			NP_751915.1
IL15	NR_037840.3	n.765-57C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-99-57C>T		intron_variant		1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94083 AN: 151180 Hom.: 29700 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.605 AC: 227431 AN: 375882 Hom.: 71478 Cov.: 0 AF XY: 0.605 AC XY: 119537 AN XY: 197708

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.622 AC: 94159 AN: 151298 Hom.: 29730 Cov.: 30 AF XY: 0.632 AC XY: 46690 AN XY: 73892

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.600

Alfa AF: 0.609 Hom.: 3197

Bravo AF: 0.625

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs1493013; hg19: chr4-142640462;