rs13143866

Positions:

• chr4-122619603-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021803.4(IL21):​c.204+1098C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,156 control chromosomes in the GnomAD database, including 4,377 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 0.23 (4377 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

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-AS1 (HGNC:40299): (IL21 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21	NM_021803.4	c.204+1098C>T		intron_variant		ENST00000648588.1
IL21-AS1	NR_104126.1	n.510+111G>A		intron_variant, non_coding_transcript_variant
IL21	NM_001207006.3	c.204+1098C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21	ENST00000648588.1	c.204+1098C>T		intron_variant			NM_021803.4	P1
IL21-AS1	ENST00000417927.1	n.510+111G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35663 AN: 152038 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.234 AC: 35680 AN: 152156 Hom.: 4377 Cov.: 32 AF XY: 0.225 AC XY: 16740 AN XY: 74384

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.242

Alfa AF: 0.229 Hom.: 1119

Bravo AF: 0.240

Asia WGS AF: 0.169 AC: 587 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs13143866; hg19: chr4-123540758;