rs10752157

Variant names:

• chr10-5943662-C-A
• rs10752157
• ENST00000620345.4:c.973G>T

Variant summary

Our verdict is Benign. The variant received -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. 7/8 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
• Publications: 5 publications found

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]

ENSG00000232807 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620345.4. 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
	LOC105376384	NR_188178.1		n.514G>T		non_coding_transcript_exon	Exon 2 of 2
	LOC105376384	NR_188179.1		n.388G>T		non_coding_transcript_exon	Exon 2 of 2
	LOC105376384	NR_188180.1		n.260+1993G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000620345.4	TSL:1	c.973G>T	p.Ala325Ser	missense	Exon 8 of 8	ENSP00000479839.1	K9N163
	ENSG00000232807	ENST00000448685.1	TSL:2	n.338G>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000232807	ENST00000454321.1	TSL:3	n.223G>T		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.300 AC: 9 AN: 30

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.135 AC: 7 AN: 52

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.296 AC: 12292 AN: 41496

American (AMR) AF: 0.411 AC: 6279 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3193 AN: 5160

South Asian (SAS) AF: 0.503 AC: 2426 AN: 4826

European-Finnish (FIN) AF: 0.236 AC: 2499 AN: 10594

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12677 AN: 67980

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.225 Hom.: 1555

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
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
PhyloP100		-0.059
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

Other links and lift over

dbSNP: rs10752157; hg19: chr10-5985625;