NM_002189.4:c.88+774A>G

Variant names:

• chr10-5976631-T-C
• rs8177636
• NM_002189.4:c.88+774A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	NM_002189.4	MANE Select	c.88+774A>G		intron	N/A	NP_002180.1
	IL15RA	NM_001256765.1		c.193+774A>G		intron	N/A	NP_001243694.1
	IL15RA	NM_001351095.2		c.262+1146A>G		intron	N/A	NP_001338024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.88+774A>G		intron	N/A	ENSP00000369312.3
	IL15RA	ENST00000397248.6	TSL:1	c.193+774A>G		intron	N/A	ENSP00000380421.3
	IL15RA	ENST00000622442.4	TSL:1	c.88+774A>G		intron	N/A	ENSP00000480949.1

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

African (AFR) AF: 0.216 AC: 8958 AN: 41420

American (AMR) AF: 0.350 AC: 5339 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3466

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5174

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3140 AN: 10544

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28433 AN: 67924

Other (OTH) AF: 0.360 AC: 757 AN: 2104

Alfa AF: 0.393 Hom.: 33047

Bravo AF: 0.333

Asia WGS AF: 0.123 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		-0.094
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: rs8177636; hg19: chr10-6018594;