rs4833837

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
IL21	NM_021803.4 link	c.234C>T	p.Cys78Cys	synonymous_variant	3/5	ENST00000648588.1	NP_068575.1	Q9HBE4-1A0A224B028
IL21	NM_001207006.3 link	c.234C>T	p.Cys78Cys	synonymous_variant	3/4		NP_001193935.1	Q9HBE4-2

Ensembl

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

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

GnomAD3 exomes

AF:

0.744

AC:

186361

AN:

250468

Hom.:

71025

AF XY:

0.741

AC XY:

100333

AN XY:

135368

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 SAS exome

AF:

0.841

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

Gnomad4 AFR exome

AF:

0.931

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.737

Gnomad4 EAS exome

AF:

0.899

Gnomad4 SAS exome

AF:

0.841

Gnomad4 FIN exome

AF:

0.556

Gnomad4 NFE exome

AF:

0.684

Gnomad4 OTH exome

AF:

0.737

GnomAD4 genome

AF:

0.769

AC:

116925

AN:

152146

Hom.:

45989

Cov.:

AF XY:

0.766

AC XY:

56958

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.743

Gnomad4 EAS

AF:

0.886

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.554

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.775

Alfa

AF:

0.708

Hom.:

76835

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 18802358) -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.2

DANN

Benign

0.75

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

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