4-141717598-T-G

Position:

• chr4-141717598-T-G

Variant summary

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

The ENST00000477265.5(IL15):​c.-2067T>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 0.481 in 152,000 control chromosomes in the GnomAD database, including 17,654 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 0.48 (17619 hom., cov: 31)
  • Exomes 𝑓: 0.49 (35 hom.)
• Consequence: IL15 ENST00000477265.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.-99-1768T>G		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-287-1780T>G		intron_variant			NP_751915.1
IL15	NR_037840.3	n.765-1768T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-99-1768T>G		intron_variant		1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72994 AN: 151634 Hom.: 17608 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.488 AC: 122 AN: 250 Hom.: 35 Cov.: 0 AF XY: 0.489 AC XY: 88 AN XY: 180

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.481 AC: 73035 AN: 151750 Hom.: 17619 Cov.: 31 AF XY: 0.487 AC XY: 36079 AN XY: 74156

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.466

Alfa AF: 0.465 Hom.: 7240

Bravo AF: 0.467

Asia WGS AF: 0.575 AC: 1996 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.55

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: rs6819823; hg19: chr4-142638751;