chr4-141733394-T-C

Position:

• chr4-141733394-T-C

Variant summary

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

The NM_000585.5(IL15):​c.*546T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,214 control chromosomes in the GnomAD database, including 42,534 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 0.74 (42517 hom., cov: 32)
  • Exomes 𝑓: 0.68 (17 hom.)
• Consequence: IL15 NM_000585.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15	NM_000585.5	c.*546T>C		3_prime_UTR_variant	8/8	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.*546T>C		3_prime_UTR_variant	10/10		NP_751915.1
IL15	NR_037840.3	n.1898T>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.*546T>C		3_prime_UTR_variant	8/8	1	NM_000585.5	ENSP00000323505	P1
IL15	ENST00000296545.11	c.*546T>C		3_prime_UTR_variant	8/8	1		ENSP00000296545	P1
IL15	ENST00000394159.2	c.*546T>C		3_prime_UTR_variant	5/5	1		ENSP00000377714
IL15	ENST00000477265.5	c.*546T>C		3_prime_UTR_variant	7/7	1		ENSP00000436914

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112557 AN: 152020 Hom.: 42462 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.720

GnomAD4 exome AF: 0.684 AC: 52 AN: 76 Hom.: 17 Cov.: 0 AF XY: 0.679 AC XY: 38 AN XY: 56

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.656

GnomAD4 genome AF: 0.741 AC: 112672 AN: 152138 Hom.: 42517 Cov.: 32 AF XY: 0.747 AC XY: 55565 AN XY: 74358

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.723

Alfa AF: 0.668 Hom.: 20381

Bravo AF: 0.748

Asia WGS AF: 0.854 AC: 2970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.60

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: rs10833; hg19: chr4-142654547;