rs4833837

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021803.4(IL21):c.234C>T(p.Cys78Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,610,618 control chromosomes in the GnomAD database, including 417,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45989 hom., cov: 33)

Exomes 𝑓: 0.71 ( 371236 hom. )

Consequence

IL21
NM_021803.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.583

Publications

47 publications found

Variant links:

Genes affected

IL21 (HGNC:6005): (interleukin 21) This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IL21 Gene-Disease associations (from GenCC):

IL21-related infantile inflammatory bowel disease
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

IL21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-122615808-G-A is Benign according to our data. Variant chr4-122615808-G-A is described in ClinVar as Benign. ClinVar VariationId is 402975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.583 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21	NM_021803.4 link	c.234C>T	p.Cys78Cys	synonymous_variant	Exon 3 of 5	ENST00000648588.1	NP_068575.1	Q9HBE4-1A0A224B028
IL21	NM_001207006.3 link	c.234C>T	p.Cys78Cys	synonymous_variant	Exon 3 of 4		NP_001193935.1	Q9HBE4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL21	ENST00000648588.1 link	c.234C>T	p.Cys78Cys	synonymous_variant	Exon 3 of 5		NM_021803.4	ENSP00000497915.1	Q9HBE4-1
IL21	ENST00000611104.2 link	c.234C>T	p.Cys78Cys	synonymous_variant	Exon 3 of 4	1		ENSP00000477555.1	Q9HBE4-2
IL21	ENST00000647784.1 link	n.86C>T		non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116798

AN:

152028

Hom.:

45926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.921

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.855

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.775

GnomAD2 exomes

AF:

0.744

AC:

186361

AN:

250468

AF XY:

0.741

show subpopulations

Gnomad AFR exome

AF:

0.929

Gnomad AMR exome

AF:

0.856

Gnomad ASJ exome

AF:

0.739

Gnomad EAS exome

AF:

0.887

Gnomad FIN exome

AF:

0.550

Gnomad NFE exome

AF:

0.673

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.709

AC:

1033909

AN:

1458472

Hom.:

371236

Cov.:

AF XY:

0.712

AC XY:

516985

AN XY:

725736

show subpopulations

African (AFR)

AF:

0.931

AC:

31116

AN:

33418

American (AMR)

AF:

0.850

AC:

37966

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

19233

AN:

26104

East Asian (EAS)

AF:

0.899

AC:

35653

AN:

39664

South Asian (SAS)

AF:

0.841

AC:

72352

AN:

86054

European-Finnish (FIN)

AF:

0.556

AC:

29649

AN:

53346

Middle Eastern (MID)

AF:

0.826

AC:

4503

AN:

5452

European-Non Finnish (NFE)

AF:

0.684

AC:

759021

AN:

1109534

Other (OTH)

AF:

0.737

AC:

44416

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

13038

26076

39113

52151

65189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19570

39140

58710

78280

97850

<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:

0.769

AC:

116925

AN:

152146

Hom.:

45989

Cov.:

AF XY:

0.766

AC XY:

56958

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.922

AC:

38296

AN:

41556

American (AMR)

AF:

0.814

AC:

12439

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

2579

AN:

3472

East Asian (EAS)

AF:

0.886

AC:

4596

AN:

5186

South Asian (SAS)

AF:

0.857

AC:

4128

AN:

4818

European-Finnish (FIN)

AF:

0.554

AC:

5845

AN:

10542

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46424

AN:

67966

Other (OTH)

AF:

0.775

AC:

1636

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1319

2638

3957

5276

6595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.720

Hom.:

124183

Bravo

AF:

0.793

Asia WGS

AF:

0.883

AC:

3069

AN:

3476

EpiCase

AF:

0.700

EpiControl

AF:

0.694

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18802358) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

IL21-related infantile inflammatory bowel disease

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.2

(source)

DANN

Benign

0.75

PhyloP100

0.58

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over