rs3093386

Positions:

chr16-27449116-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181078.3(IL21R):c.1450G>A(p.Gly484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,613,504 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 224 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 196 hom. )

Consequence

IL21R
NM_181078.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.520

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:):

IL21R-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016019344).

BP6

Variant 16-27449116-G-A is Benign according to our data. Variant chr16-27449116-G-A is described in ClinVar as [Benign]. Clinvar id is 473943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3 linkuse as main transcript	c.1450G>A	p.Gly484Ser	missense_variant	9/9	ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL21R	ENST00000337929.8 linkuse as main transcript	c.1450G>A	p.Gly484Ser	missense_variant	9/9	1	NM_181078.3	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4 linkuse as main transcript	c.1450G>A	p.Gly484Ser	missense_variant	9/9	1		ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5 linkuse as main transcript	c.1450G>A	p.Gly484Ser	missense_variant	10/10	5		ENSP00000456707.1	Q9HBE5
IL21R-AS1	ENST00000563191.1 linkuse as main transcript	n.1168C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4656

AN:

152188

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00790

AC:

1975

AN:

250086

Hom.:

AF XY:

0.00571

AC XY:

774

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.00538

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00297

AC:

4344

AN:

1461198

Hom.:

196

Cov.:

AF XY:

0.00248

AC XY:

1804

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.00622

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000674

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.0306

AC:

4660

AN:

152306

Hom.:

224

Cov.:

AF XY:

0.0294

AC XY:

2186

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00548

Hom.:

Bravo

AF:

0.0341

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0944

AC:

415

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00990

AC:

1202

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

.;.;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.74

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.78

P;P;P

Vest4

0.047

MVP

0.41

MPC

0.34

ClinPred

0.0094

GERP RS

2.6

Varity_R

0.062

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over