4-141729098-T-G

Position:

• chr4-141729098-T-G

Variant summary

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

The ENST00000320650.9(IL15):​c.241-749T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,030 control chromosomes in the GnomAD database, including 45,476 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 0.77 (45476 hom., cov: 32)
• Consequence: IL15 ENST00000320650.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.241-749T>G		intron_variant		ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.160-749T>G		intron_variant			NP_751915.1
IL15	NR_037840.3	n.1104-749T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.241-749T>G		intron_variant		1	NM_000585.5	ENSP00000323505	P1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117064 AN: 151912 Hom.: 45444 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.771 AC: 117147 AN: 152030 Hom.: 45476 Cov.: 32 AF XY: 0.775 AC XY: 57570 AN XY: 74320

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.746

Alfa AF: 0.748 Hom.: 8965

Bravo AF: 0.779

Asia WGS AF: 0.881 AC: 3063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.59

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: rs12508955; hg19: chr4-142650251;