rs3093349

Positions:

• chr16-27439438-A-G

Variant summary

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

The ENST00000337929.8(IL21R):​c.352+1751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,880 control chromosomes in the GnomAD database, including 1,822 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 0.14 (1822 hom., cov: 32)
• Consequence: IL21R ENST00000337929.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476

Genes affected

IL21R (HGNC:6006): (interleukin 21 receptor) The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2, 4, 7, 9, and 15. This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3	c.352+1751A>G		intron_variant		ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.352+1751A>G		intron_variant		1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4	c.352+1751A>G		intron_variant		1		ENSP00000379103	P1
IL21R	ENST00000564089.5	c.352+1751A>G		intron_variant		5		ENSP00000456707	P1
IL21R	ENST00000697146.1	c.352+1751A>G		intron_variant, NMD_transcript_variant				ENSP00000513135

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21011 AN: 151762 Hom.: 1812 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.139 AC: 21051 AN: 151880 Hom.: 1822 Cov.: 32 AF XY: 0.142 AC XY: 10564 AN XY: 74212

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0882

Gnomad4 ASJ AF: 0.0433

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.117

Alfa AF: 0.125 Hom.: 204

Bravo AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.53

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: rs3093349; hg19: chr16-27450759;