rs2254514

Variant names:

• chr4-141719385-T-G
• rs2254514
• NM_000585.5:c.-80T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-141719385-T-G
• chr4-141719385-T-A
• chr4-141719385-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000585.5(IL15):​c.-80T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IL15 NM_000585.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000585.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	NM_000585.5	MANE Select	c.-80T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	NP_000576.1	P40933-1
	IL15	NM_000585.5	MANE Select	c.-80T>G		5_prime_UTR	Exon 3 of 8	NP_000576.1	P40933-1
	IL15	NM_172175.3		c.-280T>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 10	NP_751915.1	P40933-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	ENST00000320650.9	TSL:1 MANE Select	c.-80T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	ENSP00000323505.4	P40933-1
	IL15	ENST00000296545.11	TSL:1	c.-80T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	ENSP00000296545.7	P40933-1
	IL15	ENST00000477265.5	TSL:1	c.-280T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000436914.1	P40933-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.63
PhyloP100		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2254514; hg19: chr4-142640538;