rs6850492

Positions:

• chr4-141716152-A-G
• chr4-141716152-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.-99-3214A>G		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-287-3226A>G		intron_variant			NP_751915.1
IL15	NR_037840.3	n.765-3214A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-99-3214A>G		intron_variant		1	NM_000585.5	ENSP00000323505	P1

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

Gnomad4 FIN exome AF: 0.966

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.629

Alfa AF: 0.586 Hom.: 44160

Bravo AF: 0.649

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.58

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: rs6850492; hg19: chr4-142637305;