4-141716152-A-G

Variant names:

• chr4-141716152-A-G
• rs6850492
• ENST00000477265.5:c.-3513A>G

Variant summary

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

The ENST00000477265.5(IL15):​c.-3513A>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 0.645 in 152,354 control chromosomes in the GnomAD database, including 32,249 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 0.64 (32160 hom., cov: 32)
  • Exomes 𝑓: 0.88 (89 hom.)
• Consequence: IL15 ENST00000477265.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 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.-99-3214A>G		intron	N/A	NP_000576.1
	IL15	NM_172175.3		c.-287-3226A>G		intron	N/A	NP_751915.1
	IL15	NR_037840.3		n.765-3214A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	ENST00000477265.5	TSL:1	c.-3513A>G		5_prime_UTR	Exon 1 of 7	ENSP00000436914.1
	IL15	ENST00000320650.9	TSL:1 MANE Select	c.-99-3214A>G		intron	N/A	ENSP00000323505.4
	IL15	ENST00000296545.11	TSL:1	c.-99-3214A>G		intron	N/A	ENSP00000296545.7

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98012 AN: 152012 Hom.: 32138 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.883 AC: 196 AN: 222 Hom.: 89 Cov.: 0 AF XY: 0.861 AC XY: 105 AN XY: 122

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.966 AC: 168 AN: 174

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.568 AC: 25 AN: 44

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.645 AC: 98082 AN: 152132 Hom.: 32160 Cov.: 32 AF XY: 0.654 AC XY: 48662 AN XY: 74372

African (AFR) AF: 0.685 AC: 28454 AN: 41518

American (AMR) AF: 0.716 AC: 10945 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4869 AN: 5154

South Asian (SAS) AF: 0.713 AC: 3437 AN: 4818

European-Finnish (FIN) AF: 0.678 AC: 7188 AN: 10594

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38886 AN: 67972

Other (OTH) AF: 0.629 AC: 1327 AN: 2110

Alfa AF: 0.597 Hom.: 106672

Bravo AF: 0.649

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.58
PhyloP100		-0.42
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: rs6850492; hg19: chr4-142637305;