Variant chr4-122612665-C-T 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.*45G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 1,330,264 control chromosomes in the GnomAD database, including 3,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 278 hom., cov: 32)

Exomes 𝑓: 0.066 ( 2922 hom. )

Consequence

IL21
NM_021803.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.176

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=-0.84).

BP6

Variant 4-122612665-C-T is Benign according to our data. Variant chr4-122612665-C-T is described in ClinVar as [Benign]. Clinvar id is 1269619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0735 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.*45G>A		3_prime_UTR_variant	5/5	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3 linkuse as main transcript	c.*162G>A		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.*45G>A	3_prime_UTR_variant	5/5		NM_021803.4	ENSP00000497915	P1	Q9HBE4-1
IL21	ENST00000647784.1 linkuse as main transcript	n.386G>A	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:

7678

AN:

152034

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0340

Gnomad FIN

AF:

0.0978

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0752

Gnomad OTH

AF:

0.0474

GnomAD3 exomes

AF:

0.0524

AC:

12896

AN:

246312

Hom.:

426

AF XY:

0.0537

AC XY:

7162

AN XY:

133306

show subpopulations

Gnomad AFR exome

AF:

0.00891

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.0500

Gnomad EAS exome

AF:

0.00196

Gnomad SAS exome

AF:

0.0333

Gnomad FIN exome

AF:

0.0911

Gnomad NFE exome

AF:

0.0724

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0655

AC:

77209

AN:

1178112

Hom.:

2922

Cov.:

AF XY:

0.0649

AC XY:

38955

AN XY:

600354

show subpopulations

Gnomad4 AFR exome

AF:

0.00965

Gnomad4 AMR exome

AF:

0.0306

Gnomad4 ASJ exome

AF:

0.0501

Gnomad4 EAS exome

AF:

0.00102

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.0745

Gnomad4 OTH exome

AF:

0.0583

GnomAD4 genome

AF:

0.0504

AC:

7672

AN:

152152

Hom.:

278

Cov.:

AF XY:

0.0510

AC XY:

3795

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.0397

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0342

Gnomad4 FIN

AF:

0.0978

Gnomad4 NFE

AF:

0.0752

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0677

Hom.:

373

Bravo

AF:

0.0437

Asia WGS

AF:

0.0160

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

-0.84

CADD

Benign

1.8

DANN

Benign

0.55

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