dbSNP rs2055979: IL21:c.204+1115G>T (chr4-122619586-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021803.4(IL21):c.204+1115G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,144 control chromosomes in the GnomAD database, including 5,221 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5220 hom., cov: 32)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

IL21
NM_021803.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

30 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 links:

IL21-AS1 (HGNC:40299): (IL21 antisense RNA 1)

IL21-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL21	NM_021803.4 link	c.204+1115G>T	intron_variant	Intron 2 of 4	ENST00000648588.1	NP_068575.1	Q9HBE4-1A0A224B028
IL21	NM_001207006.3 link	c.204+1115G>T	intron_variant	Intron 2 of 3		NP_001193935.1	Q9HBE4-2
IL21-AS1	NR_104126.1 link	n.510+94C>A	intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1 link	c.204+1115G>T		intron_variant	Intron 2 of 4		NM_021803.4	ENSP00000497915.1		Q9HBE4-1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35955

AN:

152022

Hom.:

5212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.237

AC:

35982

AN:

152140

Hom.:

5220

Cov.:

AF XY:

0.243

AC XY:

18084

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0759

AC:

3152

AN:

41520

American (AMR)

AF:

0.346

AC:

5286

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1181

AN:

3468

East Asian (EAS)

AF:

0.383

AC:

1980

AN:

5170

South Asian (SAS)

AF:

0.487

AC:

2349

AN:

4820

European-Finnish (FIN)

AF:

0.256

AC:

2706

AN:

10550

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.268

AC:

18246

AN:

68004

Other (OTH)

AF:

0.285

AC:

601

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1376

2751

4127

5502

6878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.270

Hom.:

1516

Bravo

AF:

0.235

Asia WGS

AF:

0.416

AC:

1448

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.096

(source)

DANN

Benign

0.51

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over