4-122617757-C-T

Variant names:

• chr4-122617757-C-T
• rs2221903
• NM_021803.4:c.205-1920G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021803.4(IL21):​c.205-1920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,128 control chromosomes in the GnomAD database, including 45,966 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 0.77 (45966 hom., cov: 32)
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 53 publications found

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 Gene-Disease associations (from GenCC):

• IL21-related infantile inflammatory bowel disease

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• common variable immunodeficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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 = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21	NM_021803.4	c.205-1920G>A		intron_variant	Intron 2 of 4	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3	c.205-1920G>A		intron_variant	Intron 2 of 3		NP_001193935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1	c.205-1920G>A		intron_variant	Intron 2 of 4		NM_021803.4	ENSP00000497915.1
IL21	ENST00000611104.2	c.205-1920G>A		intron_variant	Intron 2 of 3	1		ENSP00000477555.1
IL21	ENST00000647784.1	n.56+1082G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116750 AN: 152010 Hom.: 45903 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.768 AC: 116877 AN: 152128 Hom.: 45966 Cov.: 32 AF XY: 0.766 AC XY: 56927 AN XY: 74352

African (AFR) AF: 0.922 AC: 38273 AN: 41532

American (AMR) AF: 0.814 AC: 12441 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2579 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4591 AN: 5180

South Asian (SAS) AF: 0.856 AC: 4129 AN: 4822

European-Finnish (FIN) AF: 0.553 AC: 5837 AN: 10556

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46411 AN: 67960

Other (OTH) AF: 0.774 AC: 1634 AN: 2110

Alfa AF: 0.723 Hom.: 23529

Bravo AF: 0.793

Asia WGS AF: 0.883 AC: 3072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.36
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2221903; hg19: chr4-123538912;