rs8057464

chr16-27431972-A-Cchr16-27431972-A-Gchr16-27431972-A-T

Variant summary

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

The NM_181078.3(IL21R):c.49+1852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,078 control chromosomes in the GnomAD database, including 50,790 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 0.82 (50790 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.49+1852A>C		intron_variant		ENST00000337929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.49+1852A>C		intron_variant		1	NM_181078.3	P1
IL21R	ENST00000395754.4	c.49+1852A>C		intron_variant		1		P1
IL21R	ENST00000564089.5	c.49+1852A>C		intron_variant		5		P1
IL21R	ENST00000697146.1	c.49+1852A>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123944 AN: 151960 Hom.: 50749 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.816 AC: 124046 AN: 152078 Hom.: 50790 Cov.: 32 AF XY: 0.821 AC XY: 61043 AN XY: 74332

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.778

Alfa AF: 0.775 Hom.: 6333

Bravo AF: 0.809

Asia WGS AF: 0.940 AC: 3267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.41
Dann	Benign	0.13

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: rs8057464; hg19: chr16-27443293;