4-141719385-T-C

Variant names:

• chr4-141719385-T-C
• rs2254514
• NM_000585.5:c.-80T>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.-80T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 722,196 control chromosomes in the GnomAD database, including 212,165 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 (45855 hom., cov: 31)
  • Exomes 𝑓: 0.76 (166310 hom.)
• Consequence: IL15 NM_000585.5 5_prime_UTR
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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 rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-80T>C		5_prime_UTR_variant	Exon 3 of 8	ENST00000320650.9	NP_000576.1
IL15	NR_037840.3	n.784T>C		non_coding_transcript_exon_variant	Exon 3 of 8
IL15	NM_172175.3	c.-280T>C		5_prime_UTR_variant	Exon 4 of 10		NP_751915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-80T>C		5_prime_UTR_variant	Exon 3 of 8	1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117560 AN: 151932 Hom.: 45805 Cov.: 31

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.759 AC: 432730 AN: 570146 Hom.: 166310 Cov.: 4 AF XY: 0.758 AC XY: 235906 AN XY: 311110

African (AFR) AF: 0.816 AC: 11920 AN: 14600

American (AMR) AF: 0.856 AC: 28663 AN: 33472

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 13336 AN: 17792

East Asian (EAS) AF: 0.998 AC: 33600 AN: 33652

South Asian (SAS) AF: 0.796 AC: 45909 AN: 57690

European-Finnish (FIN) AF: 0.741 AC: 37790 AN: 50980

Middle Eastern (MID) AF: 0.679 AC: 2632 AN: 3878

European-Non Finnish (NFE) AF: 0.720 AC: 236001 AN: 327572

Other (OTH) AF: 0.750 AC: 22879 AN: 30510

GnomAD4 genome AF: 0.774 AC: 117665 AN: 152050 Hom.: 45855 Cov.: 31 AF XY: 0.777 AC XY: 57731 AN XY: 74298

African (AFR) AF: 0.826 AC: 34264 AN: 41490

American (AMR) AF: 0.811 AC: 12392 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2617 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5145 AN: 5178

South Asian (SAS) AF: 0.819 AC: 3936 AN: 4808

European-Finnish (FIN) AF: 0.738 AC: 7795 AN: 10558

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.722 AC: 49049 AN: 67954

Other (OTH) AF: 0.741 AC: 1561 AN: 2108

Alfa AF: 0.752 Hom.: 9627

Bravo AF: 0.782

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		0.44
Mutation Taster		=300/0	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: rs2254514; hg19: chr4-142640538;