rs10752157

Positions:

• chr10-5943662-C-A

Variant summary

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

The ENST00000620345.4(IL15RA):​c.973G>T​(p.Ala325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,226 control chromosomes in the GnomAD database, including 6,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6556 hom., cov: 32)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: IL15RA ENST00000620345.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

Genes affected

IL15RA (HGNC:5978): (interleukin 15 receptor subunit alpha) This gene encodes a cytokine receptor that specifically binds interleukin 15 (IL15) with high affinity. The receptors of IL15 and IL2 share two subunits, IL2R beta and IL2R gamma. This forms the basis of many overlapping biological activities of IL15 and IL2. The protein encoded by this gene is structurally related to IL2R alpha, an additional IL2-specific alpha subunit necessary for high affinity IL2 binding. Unlike IL2RA, IL15RA is capable of binding IL15 with high affinity independent of other subunits, which suggests distinct roles between IL15 and IL2. This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported.[provided by RefSeq, Apr 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004617363).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376384	XR_930616.4	n.260+1993G>T		intron_variant, non_coding_transcript_variant
LOC105376384	XR_001747347.2	n.514G>T		non_coding_transcript_exon_variant	2/2
LOC105376384	XR_001747345.3	n.260+1993G>T		intron_variant, non_coding_transcript_variant
LOC105376384	XR_001747346.3	n.260+1993G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000620345.4	c.973G>T	p.Ala325Ser	missense_variant	8/8	1		ENSP00000479839	A2
	ENST00000397264.4	n.246+1993G>T		intron_variant, non_coding_transcript_variant		3
	ENST00000448685.1	n.338G>T		non_coding_transcript_exon_variant	2/2	2
	ENST00000454321.1	n.223G>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41181 AN: 152014 Hom.: 6554 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.202 AC: 19 AN: 94 Hom.: 2 Cov.: 0 AF XY: 0.185 AC XY: 10 AN XY: 54

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.271 AC: 41208 AN: 152132 Hom.: 6556 Cov.: 32 AF XY: 0.285 AC XY: 21162 AN XY: 74374

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.282

Alfa AF: 0.222 Hom.: 938

Bravo AF: 0.285

TwinsUK AF: 0.184 AC: 681

ALSPAC AF: 0.189 AC: 727

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.72
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0046	T
Vest4		0.075
MVP		0.23
GERP RS		-0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10752157; hg19: chr10-5985625;