dbSNP rs6836189: IL21:c.204+515C>T (chr4-122620186-G-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+515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,730 control chromosomes in the GnomAD database, including 28,209 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 0.60 ( 28100 hom., cov: 33)

Exomes 𝑓: 0.57 ( 109 hom. )

Consequence

IL21
NM_021803.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179

Publications

6 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021803.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL21	NM_021803.4	MANE Select	c.204+515C>T	intron	N/A	NP_068575.1
IL21	NM_001207006.3		c.204+515C>T	intron	N/A	NP_001193935.1
IL21-AS1	NR_104126.1		n.708+21G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL21	ENST00000648588.1	MANE Select	c.204+515C>T	intron	N/A	ENSP00000497915.1
IL21	ENST00000611104.2	TSL:1	c.204+515C>T	intron	N/A	ENSP00000477555.1
IL21-AS1	ENST00000417927.1	TSL:1	n.708+21G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91899

AN:

151936

Hom.:

28074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.638

GnomAD4 exome

AF:

0.572

AC:

387

AN:

676

Hom.:

109

Cov.:

AF XY:

0.591

AC XY:

221

AN XY:

374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.671

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.357

AC:

AN:

South Asian (SAS)

AF:

0.625

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.568

AC:

293

AN:

516

Other (OTH)

AF:

0.389

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.605

AC:

91976

AN:

152054

Hom.:

28100

Cov.:

AF XY:

0.600

AC XY:

44563

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.664

AC:

27537

AN:

41480

American (AMR)

AF:

0.603

AC:

9202

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

2285

AN:

3468

East Asian (EAS)

AF:

0.427

AC:

2209

AN:

5168

South Asian (SAS)

AF:

0.656

AC:

3163

AN:

4818

European-Finnish (FIN)

AF:

0.484

AC:

5110

AN:

10550

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40226

AN:

67988

Other (OTH)

AF:

0.636

AC:

1344

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1901

3801

5702

7602

9503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.596

Hom.:

9598

Bravo

AF:

0.615

Asia WGS

AF:

0.564

AC:

1967

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.67

PhyloP100

0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over