Genetic Variant NM_181078.3:c.1536C>A (chr16-27449202-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181078.3(IL21R):c.1536C>A(p.Asp512Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D512D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL21R
NM_181078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

1 publications found

Variant links:

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 links:

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

IL21R-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08033481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.1536C>A	p.Asp512Glu	missense_variant	Exon 9 of 9	ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL21R	ENST00000337929.8 link	c.1536C>A	p.Asp512Glu	missense_variant	Exon 9 of 9	1	NM_181078.3	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4 link	c.1536C>A	p.Asp512Glu	missense_variant	Exon 9 of 9	1		ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5 link	c.1536C>A	p.Asp512Glu	missense_variant	Exon 10 of 10	5		ENSP00000456707.1	Q9HBE5
IL21R-AS1	ENST00000563191.1 link	n.1082G>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247254

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.0000645

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:

0.00000137

AC:

AN:

1460668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726642

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111962

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.15

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.062

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.47

.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;L;L

PhyloP100

-1.3

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.062

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.62

P;P;P

Vest4

0.084

MutPred

0.28

Gain of glycosylation at P510 (P = 0.0736);Gain of glycosylation at P510 (P = 0.0736);Gain of glycosylation at P510 (P = 0.0736);

MVP

0.56

MPC

0.39

ClinPred

0.054

GERP RS

-6.2

Varity_R

0.083

gMVP

0.094

Mutation Taster

=88/12

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over