rs179766

Positions:

• chr16-27415473-C-A
• chr16-27415473-C-G
• chr16-27415473-C-T

Variant summary

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

The NM_181078.3(IL21R):​c.-17+12855C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,228 control chromosomes in the GnomAD database, including 46,749 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 0.78 (46749 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3	c.-17+12855C>A		intron_variant		ENST00000337929.8	NP_851564.1
IL21R	NM_181079.5	c.50+12253C>A		intron_variant			NP_851565.4
IL21R	XM_011545857.4	c.50+12253C>A		intron_variant			XP_011544159.1
IL21R	XM_017023257.3	c.-146-677C>A		intron_variant			XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.-17+12855C>A		intron_variant		1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000564089.5	c.-17+12253C>A		intron_variant		5		ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117966 AN: 152110 Hom.: 46702 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.776 AC: 118071 AN: 152228 Hom.: 46749 Cov.: 32 AF XY: 0.782 AC XY: 58173 AN XY: 74408

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.717

Alfa AF: 0.670 Hom.: 2968

Bravo AF: 0.779

Asia WGS AF: 0.889 AC: 3091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.34

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: rs179766; hg19: chr16-27426794;