rs113148369

Positions:

• chr16-27448698-C-A
• chr16-27448698-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181078.3(IL21R):​c.1032C>A​(p.Asp344Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D344H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL21R NM_181078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

Genes affected

IL21R (HGNC:6006): (interleukin 21 receptor) The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2, 4, 7, 9, and 15. This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

IL21R-AS1 (HGNC:27551): (IL21R antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22575065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.1032C>A	p.Asp344Glu	missense_variant	9/9	ENST00000337929.8
IL21R-AS1	NR_037158.1	n.1586G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.1032C>A	p.Asp344Glu	missense_variant	9/9	1	NM_181078.3	P1
IL21R-AS1	ENST00000563191.1	n.1586G>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.4
DANN	Uncertain	0.97
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.089
Sift	Uncertain	0.020	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.087
MutPred		0.34		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.43
MPC		0.58
ClinPred		0.44	T
GERP RS		-5.2
Varity_R		0.068
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-27460019;