10-5963811-G-A

Variant names:

• chr10-5963811-G-A
• rs143835821
• NM_002189.4:c.314C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002189.4(IL15RA):​c.314C>T​(p.Ala105Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: IL15RA NM_002189.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.345
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05140099).
• BP6: Variant 10-5963811-G-A is Benign according to our data. Variant chr10-5963811-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3285736.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	NM_002189.4	MANE Select	c.314C>T	p.Ala105Val	missense	Exon 3 of 7	NP_002180.1	Q13261-1
	IL15RA	NM_001256765.1		c.572C>T	p.Ala191Val	missense	Exon 4 of 8	NP_001243694.1	G8CVM3
	IL15RA	NM_001243539.2		c.206C>T	p.Ala69Val	missense	Exon 3 of 7	NP_001230468.1	Q13261-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL15RA	ENST00000379977.8	TSL:1 MANE Select	c.314C>T	p.Ala105Val	missense	Exon 3 of 7	ENSP00000369312.3	Q13261-1
	IL15RA	ENST00000397248.6	TSL:1	c.572C>T	p.Ala191Val	missense	Exon 4 of 8	ENSP00000380421.3	A0A0A0MS77
	IL15RA	ENST00000622442.4	TSL:1	c.467C>T	p.Ala156Val	missense	Exon 4 of 8	ENSP00000480949.1	K9N2Q6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000526 AC: 1 AN: 189934 AF XY: 0.00

Gnomad AFR exome AF: 0.0000837

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1395196 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692788

African (AFR) AF: 0.00 AC: 0 AN: 28696

American (AMR) AF: 0.00 AC: 0 AN: 29022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24150

East Asian (EAS) AF: 0.00 AC: 0 AN: 34418

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 73990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1088642

Other (OTH) AF: 0.00 AC: 0 AN: 57734

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.2
DANN	Benign	0.86
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.34
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.035
Sift	Benign	0.65	T
Sift4G	Benign	0.54	T
Polyphen		0.017	B
Vest4		0.14
MVP		0.34
MPC		0.51
ClinPred		0.019	T
GERP RS		-1.7
PromoterAI		0.0064	Neutral
Varity_R		0.077
gMVP		0.096
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs143835821; hg19: chr10-6005774; COSMIC: COSV66093361; COSMIC: COSV66093361;