16-27402529-C-T

Position:

• chr16-27402529-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.-106C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 153,818 control chromosomes in the GnomAD database, including 953 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 0.095 (942 hom., cov: 32)
  • Exomes 𝑓: 0.093 (11 hom.)
• Consequence: IL21R NM_181078.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.-106C>T		5_prime_UTR_variant	1/9	ENST00000337929.8
IL21R	NM_181079.5	c.-181C>T		5_prime_UTR_variant	1/10
IL21R	XM_011545857.4	c.-217C>T		5_prime_UTR_variant	1/10
IL21R	XM_017023257.3	c.-236C>T		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.-106C>T		5_prime_UTR_variant	1/9	1	NM_181078.3	P1
IL21R	ENST00000564089.5	c.-247C>T		5_prime_UTR_variant	1/10	5		P1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14501 AN: 152134 Hom.: 943 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0932 AC: 146 AN: 1566 Hom.: 11 Cov.: 0 AF XY: 0.0902 AC XY: 81 AN XY: 898

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.0377

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.0909

GnomAD4 genome AF: 0.0952 AC: 14496 AN: 152252 Hom.: 942 Cov.: 32 AF XY: 0.0951 AC XY: 7079 AN XY: 74432

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.101

Alfa AF: 0.102 Hom.: 333

Bravo AF: 0.0840

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.77

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: rs961914; hg19: chr16-27413850;