rs3136614

Variant names:

• chr10-5963711-G-A
• rs3136614
• NM_002189.4:c.382+32C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-5963711-G-A
• chr10-5963711-G-C
• chr10-5963711-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256765.1(IL15RA):​c.640+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,405,840 control chromosomes in the GnomAD database, including 452,508 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 0.83 (52869 hom., cov: 32)
  • Exomes 𝑓: 0.80 (399639 hom.)
• Consequence: IL15RA NM_001256765.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256765.1. 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.382+32C>T		intron	N/A	NP_002180.1
	IL15RA	NM_001256765.1		c.640+32C>T		intron	N/A	NP_001243694.1
	IL15RA	NM_001351095.2		c.457+2434C>T		intron	N/A	NP_001338024.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.382+32C>T		intron	N/A	ENSP00000369312.3
	IL15RA	ENST00000397248.6	TSL:1	c.640+32C>T		intron	N/A	ENSP00000380421.3
	IL15RA	ENST00000622442.4	TSL:1	c.535+32C>T		intron	N/A	ENSP00000480949.1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126414 AN: 152052 Hom.: 52812 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.807

GnomAD2 exomes AF: 0.830 AC: 127055 AN: 152992 AF XY: 0.827

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.895

Gnomad ASJ exome AF: 0.804

Gnomad EAS exome AF: 0.969

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.797 AC: 999206 AN: 1253670 Hom.: 399639 Cov.: 17 AF XY: 0.799 AC XY: 496987 AN XY: 622172

African (AFR) AF: 0.879 AC: 21618 AN: 24584

American (AMR) AF: 0.876 AC: 17160 AN: 19578

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 17413 AN: 21616

East Asian (EAS) AF: 0.968 AC: 30366 AN: 31386

South Asian (SAS) AF: 0.897 AC: 58025 AN: 64712

European-Finnish (FIN) AF: 0.881 AC: 45818 AN: 51978

Middle Eastern (MID) AF: 0.805 AC: 4250 AN: 5278

European-Non Finnish (NFE) AF: 0.776 AC: 761953 AN: 982160

Other (OTH) AF: 0.813 AC: 42603 AN: 52378

GnomAD4 genome AF: 0.832 AC: 126531 AN: 152170 Hom.: 52869 Cov.: 32 AF XY: 0.838 AC XY: 62367 AN XY: 74388

African (AFR) AF: 0.880 AC: 36534 AN: 41524

American (AMR) AF: 0.840 AC: 12835 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2828 AN: 3466

East Asian (EAS) AF: 0.965 AC: 4994 AN: 5174

South Asian (SAS) AF: 0.896 AC: 4314 AN: 4816

European-Finnish (FIN) AF: 0.888 AC: 9416 AN: 10608

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53169 AN: 67986

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.792 Hom.: 91541

Bravo AF: 0.828

Asia WGS AF: 0.932 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.43
PhyloP100		-0.51
PromoterAI		-0.0058	Neutral
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: rs3136614; hg19: chr10-6005674;