4-141717598-T-G

Variant names:

• chr4-141717598-T-G
• rs6819823
• ENST00000477265.5:c.-2067T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477265.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	NM_000585.5	MANE Select	c.-99-1768T>G		intron	N/A	NP_000576.1	P40933-1
	IL15	NM_172175.3		c.-287-1780T>G		intron	N/A	NP_751915.1	P40933-2
	IL15	NR_037840.3		n.765-1768T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	ENST00000477265.5	TSL:1	c.-2067T>G		5_prime_UTR	Exon 1 of 7	ENSP00000436914.1	P40933-2
	IL15	ENST00000320650.9	TSL:1 MANE Select	c.-99-1768T>G		intron	N/A	ENSP00000323505.4	P40933-1
	IL15	ENST00000296545.11	TSL:1	c.-99-1768T>G		intron	N/A	ENSP00000296545.7	P40933-1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 2 AN: 8

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.514 AC: 109 AN: 212

Other (OTH) AF: 0.409 AC: 9 AN: 22

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

African (AFR) AF: 0.474 AC: 19601 AN: 41390

American (AMR) AF: 0.430 AC: 6558 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1948 AN: 3466

East Asian (EAS) AF: 0.532 AC: 2739 AN: 5146

South Asian (SAS) AF: 0.593 AC: 2845 AN: 4796

European-Finnish (FIN) AF: 0.554 AC: 5809 AN: 10482

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31918 AN: 67900

Other (OTH) AF: 0.466 AC: 985 AN: 2116

Alfa AF: 0.466 Hom.: 8127

Bravo AF: 0.467

Asia WGS AF: 0.575 AC: 1996 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.94
Mutation Taster		=299/1	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: rs6819823; hg19: chr4-142638751;