Variant 4-122612679-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021803.4(IL21):c.*31C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,400,228 control chromosomes in the GnomAD database, including 3,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 277 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3153 hom. )

Consequence

IL21
NM_021803.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.163

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:

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 (BayesDel_noAF=-0.79).

BP6

Variant 4-122612679-G-A is Benign according to our data. Variant chr4-122612679-G-A is described in ClinVar as [Benign]. Clinvar id is 1229892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21	NM_021803.4 linkuse as main transcript	c.*31C>T		3_prime_UTR_variant	5/5	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant	4/4		NP_001193935.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1 linkuse as main transcript	c.*31C>T	3_prime_UTR_variant	5/5		NM_021803.4	ENSP00000497915	P1	Q9HBE4-1
IL21	ENST00000647784.1 linkuse as main transcript	n.372C>T	non_coding_transcript_exon_variant	4/4
IL21	ENST00000611104.2 linkuse as main transcript		downstream_gene_variant		1		ENSP00000477555		Q9HBE4-2

Frequencies

GnomAD3 genomes

AF:

0.0505

AC:

7671

AN:

152048

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.0978

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0752

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0527

AC:

13146

AN:

249456

Hom.:

445

AF XY:

0.0541

AC XY:

7295

AN XY:

134960

show subpopulations

Gnomad AFR exome

AF:

0.00887

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.0501

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0334

Gnomad FIN exome

AF:

0.0918

Gnomad NFE exome

AF:

0.0728

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0673

AC:

83934

AN:

1248062

Hom.:

3153

Cov.:

AF XY:

0.0665

AC XY:

42064

AN XY:

632226

show subpopulations

Gnomad4 AFR exome

AF:

0.00982

Gnomad4 AMR exome

AF:

0.0307

Gnomad4 ASJ exome

AF:

0.0504

Gnomad4 EAS exome

AF:

0.000674

Gnomad4 SAS exome

AF:

0.0342

Gnomad4 FIN exome

AF:

0.0879

Gnomad4 NFE exome

AF:

0.0764

Gnomad4 OTH exome

AF:

0.0592

GnomAD4 genome

AF:

0.0504

AC:

7665

AN:

152166

Hom.:

277

Cov.:

AF XY:

0.0509

AC XY:

3789

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.0397

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0338

Gnomad4 FIN

AF:

0.0978

Gnomad4 NFE

AF:

0.0752

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0676

Hom.:

399

Bravo

AF:

0.0437

Asia WGS

AF:

0.0130

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

DANN

Benign

0.72

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