chr4-141694592-C-T

Position:

• chr4-141694592-C-T

Variant summary

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

The NM_000585.5(IL15):​c.-99-24774C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,074 control chromosomes in the GnomAD database, including 1,546 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 0.11 (1546 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.-99-24774C>T		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-288+5557C>T		intron_variant			NP_751915.1
IL15	NR_037840.3	n.765-24774C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-99-24774C>T		intron_variant		1	NM_000585.5	ENSP00000323505	P1
IL15	ENST00000296545.11	c.-99-24774C>T		intron_variant		1		ENSP00000296545	P1
IL15	ENST00000514653.5	c.-288+5557C>T		intron_variant		5		ENSP00000422271
IL15	ENST00000529613.5	c.-100+5557C>T		intron_variant		5		ENSP00000435462	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16643 AN: 151958 Hom.: 1544 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.109 AC: 16646 AN: 152074 Hom.: 1546 Cov.: 32 AF XY: 0.116 AC XY: 8602 AN XY: 74320

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.117

Alfa AF: 0.102 Hom.: 454

Bravo AF: 0.121

Asia WGS AF: 0.218 AC: 760 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.29

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: rs13106911; hg19: chr4-142615745;