10-5968664-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000300557 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351096.1. 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
	IL15RA	NM_002189.4	MANE Select	c.89-2325A>T		intron	N/A	NP_002180.1	Q13261-1
	IL15RA	NM_001351096.1		c.-91A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001338025.1
	IL15RA	NM_001351096.1		c.-91A>T		5_prime_UTR	Exon 2 of 8	NP_001338025.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.89-2325A>T		intron	N/A	ENSP00000369312.3	Q13261-1
	IL15RA	ENST00000397248.6	TSL:1	c.346+112A>T		intron	N/A	ENSP00000380421.3	A0A0A0MS77
	IL15RA	ENST00000622442.4	TSL:1	c.241+112A>T		intron	N/A	ENSP00000480949.1	K9N2Q6

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

African (AFR) AF: 0.152 AC: 2178 AN: 14366

American (AMR) AF: 0.227 AC: 6693 AN: 29424

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2411 AN: 16636

East Asian (EAS) AF: 0.303 AC: 9526 AN: 31442

South Asian (SAS) AF: 0.135 AC: 7173 AN: 53214

European-Finnish (FIN) AF: 0.104 AC: 3237 AN: 31042

Middle Eastern (MID) AF: 0.147 AC: 393 AN: 2666

European-Non Finnish (NFE) AF: 0.106 AC: 30602 AN: 287690

Other (OTH) AF: 0.127 AC: 3560 AN: 28048

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

African (AFR) AF: 0.149 AC: 6201 AN: 41492

American (AMR) AF: 0.198 AC: 3033 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1597 AN: 5184

South Asian (SAS) AF: 0.133 AC: 640 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7379 AN: 67996

Other (OTH) AF: 0.140 AC: 295 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.58
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8177676; hg19: chr10-6010627;