chr10-5966650-C-T

Position:

• chr10-5966650-C-T

Variant summary

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

The NM_002189.4(IL15RA):​c.89-311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 151,816 control chromosomes in the GnomAD database, including 55,948 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 0.86 (55948 hom., cov: 28)
• Consequence: IL15RA NM_002189.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

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]

LOC107984200 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.89-311G>A		intron_variant		ENST00000379977.8	NP_002180.1
LOC107984200	XR_001747348.2	n.1458+2329C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.89-311G>A		intron_variant		1	NM_002189.4	ENSP00000369312	A2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 129854 AN: 151696 Hom.: 55907 Cov.: 28

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.856 AC: 129957 AN: 151816 Hom.: 55948 Cov.: 28 AF XY: 0.848 AC XY: 62889 AN XY: 74162

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.883

Alfa AF: 0.888 Hom.: 74809

Bravo AF: 0.868

Asia WGS AF: 0.747 AC: 2586 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.83
DANN	Benign	0.58

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: rs8177685; hg19: chr10-6008613;