rs6836189

Positions:

• chr4-122620186-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+515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,730 control chromosomes in the GnomAD database, including 28,209 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 0.60 (28100 hom., cov: 33)
  • Exomes 𝑓: 0.57 (109 hom.)
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21	NM_021803.4	c.204+515C>T		intron_variant		ENST00000648588.1	NP_068575.1
IL21-AS1	NR_104126.1	n.708+21G>A		intron_variant, non_coding_transcript_variant
IL21	NM_001207006.3	c.204+515C>T		intron_variant			NP_001193935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1	c.204+515C>T		intron_variant			NM_021803.4	ENSP00000497915	P1
IL21-AS1	ENST00000417927.1	n.708+21G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91899 AN: 151936 Hom.: 28074 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.572 AC: 387 AN: 676 Hom.: 109 Cov.: 0 AF XY: 0.591 AC XY: 221 AN XY: 374

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.605 AC: 91976 AN: 152054 Hom.: 28100 Cov.: 33 AF XY: 0.600 AC XY: 44563 AN XY: 74288

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.636

Alfa AF: 0.597 Hom.: 5716

Bravo AF: 0.615

Asia WGS AF: 0.564 AC: 1967 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	1.2
DANN	Benign	0.67

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: rs6836189; hg19: chr4-123541341;