rs141171117

Variant names:

• chr10-5953184-C-T
• rs141171117
• NM_002189.4:c.715G>A
• IL15RA p.Val239Ile

Your query was ambiguous. Multiple possible variants found:

• chr10-5953184-C-T
• chr10-5953184-C-A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_StrongBP6_Strong

The NM_002189.4(IL15RA):c.715G>A (p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000795 (AC=1,284) in the gnomAD database across 1,614,152 control chromosomes, including 8 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0107. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (3 hom.)
• Consequence: IL15RA NM_002189.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.613
• Publications: 3 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).
	BS2Observed in healthy adult		≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 8.; Very high cumulative gnomAD AC = 1284 (any gene).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IL15RA NM_002189.4	MANE Select	c.715G>A p.Val239Ile	missense	Exon 7 of 7	Prot: NP_002180.1 UniProt:
	IL15RA NM_001256765.1		c.973G>A p.Val325Ile	missense	Exon 8 of 8	Prot: NP_001243694.1 UniProt:
	IL15RA NM_172200.3		c.616G>A p.Val206Ile	missense	Exon 6 of 6	Prot: NP_751950.2 UniProt:

IL15RA NM_002189.4

MANE Select

HGVSc / HGVSpc.715G>Ap.Val239Ile

Exon rankExon 7 of 7

missense

Prot: NP_002180.1UniProt: Q13261-1

IL15RA NM_001256765.1

HGVSc / HGVSpc.973G>Ap.Val325Ile

Exon rankExon 8 of 8

missense

Prot: NP_001243694.1UniProt: Q13261G8CVM3A0A0A0MS77

IL15RA NM_172200.3

HGVSc / HGVSpc.616G>Ap.Val206Ile

Exon rankExon 6 of 6

missense

Prot: NP_751950.2UniProt: Q13261-3

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IL15RA ENST00000379977.8	TSL:1MANE Select	c.715G>A p.Val239Ile	missense	Exon 7 of 7	Prot: ENSP00000369312.3 UniProt:
	IL15RA ENST00000397248.6	TSL:1	c.973G>A p.Val325Ile	missense	Exon 8 of 8	Prot: ENSP00000380421.3 UniProt:
	IL15RA ENST00000525219.6	TSL:1	c.607G>A p.Val203Ile	missense	Exon 7 of 7	Prot: ENSP00000431529.2 UniProt:

IL15RA ENST00000379977.8

TSL:1MANE Select

HGVSc / HGVSpc.715G>Ap.Val239Ile

Exon rankExon 7 of 7

missense

Prot: ENSP00000369312.3UniProt: Q13261-1

IL15RA ENST00000397248.6

TSL:1

HGVSc / HGVSpc.973G>Ap.Val325Ile

Exon rankExon 8 of 8

missense

Prot: ENSP00000380421.3UniProt: A0A0A0MS77

IL15RA ENST00000525219.6

TSL:1

HGVSc / HGVSpc.607G>Ap.Val203Ile

Exon rankExon 7 of 7

missense

Prot: ENSP00000431529.2UniProt: Q13261-10

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00359	AC:547	Hom:5	AN:152222	Cov:33
GnomAD2 exomes	AF: 0.00122	AC:304	Hom:	AN:249130	Cov:
GnomAD4 exome	AF: 0.000504	AC:737	Hom:3	AN:1461812	Cov:31
GnomAD4 genome	AF: 0.00359	AC:547	Hom:5	AN:152340	Cov:33
TOPMed (Bravo)	AF: 0.00409	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00170	AC:538	Hom:5	AN:317200	Cov:
Local & regional cohorts 8 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.00342	AC:8	Hom:0	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.000295	AC:	Hom:	AN:	Cov:
ESP6500 (Exome Variant Server)	AF: 0.00384	AC:50	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.00144	AC:5	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.000553	AC:4	Hom:	AN:7234	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.000367	AC:45	Hom:0	AN:122576	Cov:
UK10K	AF: 0.000132	AC:1	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.000335	AC:3	Hom:0	AN:8960	Cov:

Showing 14 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.000416 *	4	9622	0.000288 *	3	10428
BipEx(Bipolar disorder (including schizoaffective))	0.000246	7	28420	0.000173	5	28844
Epi25(Epilepsy)	0.00112	47	41958	0.00117	78	66888
SCHEMA(Schizophrenia)	0.00210	256	122070	0.00176	336	190924

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.4
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.67
DANN	Benign	0.59
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0077	N
FuncVEP CTI	Benign	0.00094
GPN-Star LLR	N/A	0.75
GPN-Star score	N/A	0.60
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
Mutation Taster	N/A	99/1	polymorphism
MutationAssessor	Benign	0.69	N
PhyloP100	Benign	-0.61
popEVE	Benign	-3.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.37	N
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.0
REVEL	Benign	0.015
Sift	Benign	0.41	T
Sift4G	Benign	0.48	T
Varity_R	N/A	0.011
VESM-3B	Benign	-4.5

Showing 29 of 29 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.030
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs141171117;

hg19: chr10-5995147;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar