rs2322262

chr4-141654113-G-Achr4-141654113-G-Cchr4-141654113-G-T

Variant summary

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

The NM_000585.5(IL15):c.-221-2073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,152 control chromosomes in the GnomAD database, including 43,599 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 0.76 (43599 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL15	NM_000585.5	c.-221-2073G>A		intron_variant		ENST00000320650.9
IL15	NM_172175.3	c.-623-2073G>A		intron_variant
IL15	NR_037840.3	n.643-2073G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15	ENST00000320650.9	c.-221-2073G>A		intron_variant		1	NM_000585.5	P1
IL15	ENST00000296545.11	c.-221-2073G>A		intron_variant		1		P1
IL15	ENST00000514653.5	c.-623-2073G>A		intron_variant		5
IL15	ENST00000529613.5	c.-314+16889G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114812 AN: 152036 Hom.: 43562 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.755 AC: 114902 AN: 152152 Hom.: 43599 Cov.: 32 AF XY: 0.759 AC XY: 56451 AN XY: 74382

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.717

Alfa AF: 0.734 Hom.: 57508

Bravo AF: 0.760

Asia WGS AF: 0.879 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.3
Dann	Benign	0.65

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: rs2322262; hg19: chr4-142575266;