4-122613898-C-T

Variant names:

• chr4-122613898-C-T
• rs907715
• NM_021803.4:c.361-970G>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.361-970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,950 control chromosomes in the GnomAD database, including 9,419 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 0.35 (9419 hom., cov: 32)
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 68 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21	NM_021803.4	MANE Select	c.361-970G>A		intron	N/A	NP_068575.1	Q9HBE4-1
	IL21	NM_001207006.3		c.361-970G>A		intron	N/A	NP_001193935.1	Q9HBE4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21	ENST00000648588.1	MANE Select	c.361-970G>A		intron	N/A	ENSP00000497915.1	Q9HBE4-1
	IL21	ENST00000611104.2	TSL:1	c.361-970G>A		intron	N/A	ENSP00000477555.1	Q9HBE4-2
	IL21	ENST00000647784.1		n.213-970G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52561 AN: 151832 Hom.: 9406 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.346 AC: 52619 AN: 151950 Hom.: 9419 Cov.: 32 AF XY: 0.340 AC XY: 25260 AN XY: 74244

African (AFR) AF: 0.390 AC: 16166 AN: 41414

American (AMR) AF: 0.372 AC: 5684 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3464

East Asian (EAS) AF: 0.454 AC: 2342 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1448 AN: 4820

European-Finnish (FIN) AF: 0.199 AC: 2103 AN: 10548

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22565 AN: 67952

Other (OTH) AF: 0.333 AC: 704 AN: 2112

Alfa AF: 0.331 Hom.: 2007

Bravo AF: 0.363

Asia WGS AF: 0.375 AC: 1299 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-1.3
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: rs907715; hg19: chr4-123535053;