rs11930631

Variant names:

• chr4-122614140-G-A
• rs11930631
• NM_021803.4:c.361-1212C>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.361-1212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 151,992 control chromosomes in the GnomAD database, including 1,917 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 0.088 (1917 hom., cov: 32)
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 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.361-1212C>T		intron	N/A	NP_068575.1	Q9HBE4-1
	IL21	NM_001207006.3		c.361-1212C>T		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.361-1212C>T		intron	N/A	ENSP00000497915.1	Q9HBE4-1
	IL21	ENST00000611104.2	TSL:1	c.361-1212C>T		intron	N/A	ENSP00000477555.1	Q9HBE4-2
	IL21	ENST00000647784.1		n.213-1212C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13368 AN: 151874 Hom.: 1914 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0881 AC: 13385 AN: 151992 Hom.: 1917 Cov.: 32 AF XY: 0.0860 AC XY: 6388 AN XY: 74282

African (AFR) AF: 0.299 AC: 12363 AN: 41414

American (AMR) AF: 0.0300 AC: 458 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.0456 AC: 235 AN: 5154

South Asian (SAS) AF: 0.0198 AC: 95 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 67992

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0791 Hom.: 237

Bravo AF: 0.0993

Asia WGS AF: 0.0610 AC: 213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.50
PhyloP100		-0.30
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: rs11930631; hg19: chr4-123535295;