10-5976631-T-C

Position:

• chr10-5976631-T-C

Variant summary

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

The NM_002189.4(IL15RA):​c.88+774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,912 control chromosomes in the GnomAD database, including 9,349 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 0.33 (9349 hom., cov: 31)
• Consequence: IL15RA NM_002189.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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]

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 (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL15RA	NM_002189.4	c.88+774A>G		intron_variant		ENST00000379977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL15RA	ENST00000379977.8	c.88+774A>G		intron_variant		1	NM_002189.4	A2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50160 AN: 151794 Hom.: 9347 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50176 AN: 151912 Hom.: 9349 Cov.: 31 AF XY: 0.321 AC XY: 23798 AN XY: 74226

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.00696

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.360

Alfa AF: 0.408 Hom.: 20803

Bravo AF: 0.333

Asia WGS AF: 0.123 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.63

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: rs8177636; hg19: chr10-6018594;