rs1057972

Variant names:

• chr4-141733279-A-T
• rs1057972
• NM_000585.5:c.*431A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

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.*431A>T		3_prime_UTR	Exon 8 of 8	NP_000576.1	P40933-1
	IL15	NM_172175.3		c.*431A>T		3_prime_UTR	Exon 10 of 10	NP_751915.1	P40933-2
	IL15	NR_037840.3		n.1783A>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15	ENST00000320650.9	TSL:1 MANE Select	c.*431A>T		3_prime_UTR	Exon 8 of 8	ENSP00000323505.4	P40933-1
	IL15	ENST00000296545.11	TSL:1	c.*431A>T		3_prime_UTR	Exon 8 of 8	ENSP00000296545.7	P40933-1
	IL15	ENST00000394159.2	TSL:1	c.*431A>T		3_prime_UTR	Exon 5 of 5	ENSP00000377714.1	P40933-2

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

African (AFR) AF: 0.571 AC: 16 AN: 28

American (AMR) AF: 0.375 AC: 15 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 27 AN: 50

East Asian (EAS) AF: 0.405 AC: 17 AN: 42

South Asian (SAS) AF: 0.529 AC: 73 AN: 138

European-Finnish (FIN) AF: 0.560 AC: 65 AN: 116

Middle Eastern (MID) AF: 0.500 AC: 6 AN: 12

European-Non Finnish (NFE) AF: 0.454 AC: 1021 AN: 2250

Other (OTH) AF: 0.484 AC: 89 AN: 184

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

African (AFR) AF: 0.656 AC: 27194 AN: 41476

American (AMR) AF: 0.448 AC: 6849 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1948 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2738 AN: 5156

South Asian (SAS) AF: 0.597 AC: 2880 AN: 4826

European-Finnish (FIN) AF: 0.558 AC: 5887 AN: 10558

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.471 AC: 32003 AN: 67966

Other (OTH) AF: 0.511 AC: 1077 AN: 2108

Alfa AF: 0.509 Hom.: 2606

Bravo AF: 0.527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.85
PhyloP100		-1.0
Mutation Taster		=99/1	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: rs1057972; hg19: chr4-142654432;