rs1057972

Positions:

• chr4-141733279-A-T

Variant summary

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

The NM_000585.5(IL15):​c.*431A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 154,902 control chromosomes in the GnomAD database, including 22,563 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 0.53 (22214 hom., cov: 32)
  • Exomes 𝑓: 0.46 (349 hom.)
• Consequence: IL15 NM_000585.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL15	NM_000585.5	c.*431A>T		3_prime_UTR_variant	8/8	ENST00000320650.9
IL15	NM_172175.3	c.*431A>T		3_prime_UTR_variant	10/10
IL15	NR_037840.3	n.1783A>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15	ENST00000320650.9	c.*431A>T		3_prime_UTR_variant	8/8	1	NM_000585.5	P1
IL15	ENST00000296545.11	c.*431A>T		3_prime_UTR_variant	8/8	1		P1
IL15	ENST00000394159.2	c.*431A>T		3_prime_UTR_variant	5/5	1
IL15	ENST00000477265.5	c.*431A>T		3_prime_UTR_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81153 AN: 151924 Hom.: 22195 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.465 AC: 1329 AN: 2860 Hom.: 349 Cov.: 0 AF XY: 0.472 AC XY: 731 AN XY: 1550

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.534 AC: 81214 AN: 152042 Hom.: 22214 Cov.: 32 AF XY: 0.538 AC XY: 39950 AN XY: 74312

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.511

Alfa AF: 0.509 Hom.: 2606

Bravo AF: 0.527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.85

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: rs1057972; hg19: chr4-142654432;