rs2322262

Variant names:

• chr4-141654113-G-A
• rs2322262
• NM_000585.5:c.-221-2073G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-141654113-G-A
• chr4-141654113-G-C
• chr4-141654113-G-T

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000295574 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-221-2073G>A		intron_variant	Intron 1 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-623-2073G>A		intron_variant	Intron 1 of 9		NP_751915.1
IL15	NR_037840.3	n.643-2073G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-221-2073G>A		intron_variant	Intron 1 of 7	1	NM_000585.5	ENSP00000323505.4

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

African (AFR) AF: 0.758 AC: 31482 AN: 41510

American (AMR) AF: 0.786 AC: 12012 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2623 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5125 AN: 5162

South Asian (SAS) AF: 0.822 AC: 3959 AN: 4816

European-Finnish (FIN) AF: 0.740 AC: 7833 AN: 10586

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49455 AN: 68014

Other (OTH) AF: 0.717 AC: 1515 AN: 2114

Alfa AF: 0.736 Hom.: 70558

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
PhyloP100		-0.34
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: rs2322262; hg19: chr4-142575266;