rs17879298

Variant names:

• chr4-122612679-G-A
• rs17879298
• NM_021803.4:c.*31C>T

Variant summary

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

The NM_021803.4(IL21):​c.*31C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,400,228 control chromosomes in the GnomAD database, including 3,430 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 0.050 (277 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3153 hom.)
• Consequence: IL21 NM_021803.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.163
• Publications: 11 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21	NM_021803.4	c.*31C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3	c.*148C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001193935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1	c.*31C>T		3_prime_UTR_variant	Exon 5 of 5		NM_021803.4	ENSP00000497915.1
IL21	ENST00000647784.1	n.372C>T		non_coding_transcript_exon_variant	Exon 4 of 4
IL21	ENST00000611104.2	c.*148C>T		downstream_gene_variant		1		ENSP00000477555.1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7671 AN: 152048 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0527 AC: 13146 AN: 249456 AF XY: 0.0541

Gnomad AFR exome AF: 0.00887

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0501

Gnomad EAS exome AF: 0.00131

Gnomad FIN exome AF: 0.0918

Gnomad NFE exome AF: 0.0728

Gnomad OTH exome AF: 0.0592

GnomAD4 exome AF: 0.0673 AC: 83934 AN: 1248062 Hom.: 3153 Cov.: 19 AF XY: 0.0665 AC XY: 42064 AN XY: 632226

African (AFR) AF: 0.00982 AC: 287 AN: 29230

American (AMR) AF: 0.0307 AC: 1365 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 1252 AN: 24864

East Asian (EAS) AF: 0.000674 AC: 26 AN: 38604

South Asian (SAS) AF: 0.0342 AC: 2796 AN: 81840

European-Finnish (FIN) AF: 0.0879 AC: 4571 AN: 51974

Middle Eastern (MID) AF: 0.0547 AC: 294 AN: 5378

European-Non Finnish (NFE) AF: 0.0764 AC: 70188 AN: 918382

Other (OTH) AF: 0.0592 AC: 3155 AN: 53312

GnomAD4 genome AF: 0.0504 AC: 7665 AN: 152166 Hom.: 277 Cov.: 32 AF XY: 0.0509 AC XY: 3789 AN XY: 74372

African (AFR) AF: 0.0103 AC: 429 AN: 41532

American (AMR) AF: 0.0397 AC: 608 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4826

European-Finnish (FIN) AF: 0.0978 AC: 1033 AN: 10558

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5110 AN: 67986

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0648 Hom.: 479

Bravo AF: 0.0437

Asia WGS AF: 0.0130 AC: 47 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.16
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: rs17879298; hg19: chr4-123533834;