16-27421414-C-T

Position:

• chr16-27421414-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.-16-8642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 148,370 control chromosomes in the GnomAD database, including 9,965 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 0.36 (9965 hom., cov: 29)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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 = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.-16-8642C>T		intron_variant		ENST00000337929.8
IL21R	NM_181079.5	c.51-8642C>T		intron_variant
IL21R	XM_011545857.4	c.51-8642C>T		intron_variant
IL21R	XM_017023257.3	c.-17+5135C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.-16-8642C>T		intron_variant		1	NM_181078.3	P1
IL21R	ENST00000564089.5	c.-16-8642C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 53579 AN: 148280 Hom.: 9957 Cov.: 29

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.361 AC: 53617 AN: 148370 Hom.: 9965 Cov.: 29 AF XY: 0.368 AC XY: 26522 AN XY: 72008

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.353

Alfa AF: 0.337 Hom.: 4169

Bravo AF: 0.358

Asia WGS AF: 0.485 AC: 1683 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.62

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: rs2040790; hg19: chr16-27432735;