rs963154

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181078.3(IL21R):c.785+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,578,392 control chromosomes in the GnomAD database, including 74,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9550 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65201 hom. )

Consequence

IL21R
NM_181078.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.31

Publications

5 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 Gene-Disease associations (from GenCC):

immunodeficiency disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cryptosporidiosis-chronic cholangitis-liver disease syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

IL21R links:

ENSG00000308281 (HGNC:):

ENSG00000308281 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-27445292-G-C is Benign according to our data. Variant chr16-27445292-G-C is described in ClinVar as Benign. ClinVar VariationId is 1170239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL21R	NM_181078.3	MANE Select	c.785+16G>C	intron	N/A	NP_851564.1	Q9HBE5
IL21R	NM_181079.5		c.851+16G>C	intron	N/A	NP_851565.4
IL21R	NM_021798.4		c.785+16G>C	intron	N/A	NP_068570.1	Q9HBE5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL21R	ENST00000337929.8	TSL:1 MANE Select	c.785+16G>C	intron	N/A	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4	TSL:1	c.785+16G>C	intron	N/A	ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5	TSL:5	c.785+16G>C	intron	N/A	ENSP00000456707.1	Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52146

AN:

151846

Hom.:

9515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.275

AC:

68071

AN:

247774

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.0954

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.295

AC:

420978

AN:

1426428

Hom.:

65201

Cov.:

AF XY:

0.289

AC XY:

205849

AN XY:

711470

show subpopulations

African (AFR)

AF:

0.494

AC:

16186

AN:

32790

American (AMR)

AF:

0.252

AC:

11173

AN:

44374

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7385

AN:

25842

East Asian (EAS)

AF:

0.120

AC:

4749

AN:

39534

South Asian (SAS)

AF:

0.123

AC:

10506

AN:

85172

European-Finnish (FIN)

AF:

0.338

AC:

18028

AN:

53278

Middle Eastern (MID)

AF:

0.286

AC:

1621

AN:

5674

European-Non Finnish (NFE)

AF:

0.309

AC:

333836

AN:

1080514

Other (OTH)

AF:

0.295

AC:

17494

AN:

59250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14521

29042

43564

58085

72606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10650

21300

31950

42600

53250

<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

AF:

0.344

AC:

52217

AN:

151964

Hom.:

9550

Cov.:

AF XY:

0.344

AC XY:

25517

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.480

AC:

19853

AN:

41380

American (AMR)

AF:

0.294

AC:

4495

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

940

AN:

3468

East Asian (EAS)

AF:

0.106

AC:

547

AN:

5172

South Asian (SAS)

AF:

0.124

AC:

596

AN:

4824

European-Finnish (FIN)

AF:

0.342

AC:

3613

AN:

10568

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.312

AC:

21187

AN:

67954

Other (OTH)

AF:

0.323

AC:

683

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1720

3440

5160

6880

8600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.241

Hom.:

882

Bravo

AF:

0.346

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cryptosporidiosis-chronic cholangitis-liver disease syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.35

(source)

DANN

Benign

0.69

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over