4-141719309-C-T

Variant names:

• chr4-141719309-C-T
• rs1493013
• ENST00000477265.5:c.-356C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 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.-99-57C>T		intron	N/A	NP_000576.1	P40933-1
	IL15	NM_172175.3		c.-287-69C>T		intron	N/A	NP_751915.1	P40933-2
	IL15	NR_037840.3		n.765-57C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	ENST00000477265.5	TSL:1	c.-356C>T		5_prime_UTR	Exon 1 of 7	ENSP00000436914.1	P40933-2
	IL15	ENST00000320650.9	TSL:1 MANE Select	c.-99-57C>T		intron	N/A	ENSP00000323505.4	P40933-1
	IL15	ENST00000296545.11	TSL:1	c.-99-57C>T		intron	N/A	ENSP00000296545.7	P40933-1

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

African (AFR) AF: 0.575 AC: 5651 AN: 9830

American (AMR) AF: 0.719 AC: 8787 AN: 12218

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 7160 AN: 11460

East Asian (EAS) AF: 0.938 AC: 25216 AN: 26876

South Asian (SAS) AF: 0.630 AC: 15968 AN: 25348

European-Finnish (FIN) AF: 0.659 AC: 26330 AN: 39974

Middle Eastern (MID) AF: 0.563 AC: 1858 AN: 3300

European-Non Finnish (NFE) AF: 0.549 AC: 123375 AN: 224690

Other (OTH) AF: 0.590 AC: 13086 AN: 22186

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

African (AFR) AF: 0.613 AC: 25295 AN: 41236

American (AMR) AF: 0.705 AC: 10719 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3464

East Asian (EAS) AF: 0.945 AC: 4844 AN: 5128

South Asian (SAS) AF: 0.712 AC: 3419 AN: 4804

European-Finnish (FIN) AF: 0.675 AC: 7047 AN: 10434

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38610 AN: 67720

Other (OTH) AF: 0.600 AC: 1263 AN: 2106

Alfa AF: 0.613 Hom.: 5985

Bravo AF: 0.625

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.28
Mutation Taster		=300/0	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: rs1493013; hg19: chr4-142640462;