Variant 4-122612707-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_021803.4(IL21):c.*3A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,600,320 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 32 hom. )

Consequence

IL21
NM_021803.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.381

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 4-122612707-T-G is Benign according to our data. Variant chr4-122612707-T-G is described in ClinVar as [Benign]. Clinvar id is 3055532.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00253 (386/152294) while in subpopulation EAS AF= 0.0249 (129/5182). AF 95% confidence interval is 0.0214. There are 2 homozygotes in gnomad4. There are 235 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21	NM_021803.4 linkuse as main transcript	c.*3A>C		3_prime_UTR_variant	5/5	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3 linkuse as main transcript	c.*120A>C		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.*3A>C	3_prime_UTR_variant	5/5		NM_021803.4	ENSP00000497915	P1	Q9HBE4-1
IL21	ENST00000647784.1 linkuse as main transcript	n.344A>C	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:

0.00253

AC:

385

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00395

AC:

989

AN:

250506

Hom.:

AF XY:

0.00396

AC XY:

537

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0238

Gnomad SAS exome

AF:

0.00536

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.000459

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00170

AC:

2465

AN:

1448026

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1345

AN XY:

721504

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000461

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.00595

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152294

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0249

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000643

Hom.:

Bravo

AF:

0.00133

Asia WGS

AF:

0.0140

AC:

AN:

3476

EpiCase

AF:

0.000382

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL21-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.7

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