rs8177676

Variant names:

• chr10-5968664-T-A
• rs8177676
• NM_002189.4:c.89-2325A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-5968664-T-A
• chr10-5968664-T-G

Variant summary

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

The NM_001351096.1(IL15RA):​c.-91A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 646,684 control chromosomes in the GnomAD database, including 7,046 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 0.14 (1652 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5394 hom.)
• Consequence: IL15RA NM_001351096.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15RA	NM_002189.4	c.89-2325A>T		intron_variant	Intron 1 of 6	ENST00000379977.8	NP_002180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15RA	ENST00000379977.8	c.89-2325A>T		intron_variant	Intron 1 of 6	1	NM_002189.4	ENSP00000369312.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20934 AN: 152038 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.133 AC: 65773 AN: 494528 Hom.: 5394 Cov.: 0 AF XY: 0.132 AC XY: 34654 AN XY: 263494

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.138 AC: 20984 AN: 152156 Hom.: 1652 Cov.: 32 AF XY: 0.141 AC XY: 10515 AN XY: 74382

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.140

Alfa AF: 0.118 Hom.: 146

Bravo AF: 0.148

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
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: rs8177676; hg19: chr10-6010627;