4-141643936-T-C

Variant names:

• chr4-141643936-T-C
• rs1589241
• NM_000585.5:c.-222+7188T>C

Variant summary

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

The NM_000585.5(IL15):​c.-222+7188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 151,210 control chromosomes in the GnomAD database, including 45,698 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 0.78 (45698 hom., cov: 27)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 12 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=-0.87).
• 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.-222+7188T>C		intron_variant	Intron 1 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-624+7188T>C		intron_variant	Intron 1 of 9		NP_751915.1
IL15	NR_037840.3	n.642+6712T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-222+7188T>C		intron_variant	Intron 1 of 7	1	NM_000585.5	ENSP00000323505.4
IL15	ENST00000296545.11	c.-222+6712T>C		intron_variant	Intron 1 of 7	1		ENSP00000296545.7
IL15	ENST00000529613.5	c.-314+6712T>C		intron_variant	Intron 1 of 7	5		ENSP00000435462.1
IL15	ENST00000514653.5	c.-624+7188T>C		intron_variant	Intron 1 of 9	5		ENSP00000422271.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117094 AN: 151092 Hom.: 45660 Cov.: 27

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.775 AC: 117189 AN: 151210 Hom.: 45698 Cov.: 27 AF XY: 0.778 AC XY: 57417 AN XY: 73782

African (AFR) AF: 0.827 AC: 34036 AN: 41174

American (AMR) AF: 0.795 AC: 12013 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2622 AN: 3466

East Asian (EAS) AF: 0.993 AC: 5057 AN: 5094

South Asian (SAS) AF: 0.826 AC: 3957 AN: 4792

European-Finnish (FIN) AF: 0.739 AC: 7684 AN: 10392

Middle Eastern (MID) AF: 0.659 AC: 191 AN: 290

European-Non Finnish (NFE) AF: 0.728 AC: 49382 AN: 67868

Other (OTH) AF: 0.733 AC: 1542 AN: 2104

Alfa AF: 0.750 Hom.: 33723

Bravo AF: 0.782

Asia WGS AF: 0.886 AC: 3080 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	0.21
DANN	Benign	0.70
PhyloP100		-2.0
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: rs1589241; hg19: chr4-142565089;