16-27429962-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):c.-16-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,047,690 control chromosomes in the GnomAD database, including 333,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47785 hom., cov: 29)
  • Exomes 𝑓: 0.80 (286145 hom.)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.924

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-27429962-A-G is Benign according to our data. Variant chr16-27429962-A-G is described in ClinVar as [Benign]. Clinvar id is 1241251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.-16-94A>G		intron_variant		ENST00000337929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.-16-94A>G		intron_variant		1	NM_181078.3	P1
IL21R	ENST00000395754.4	c.-16-94A>G		intron_variant		1		P1
IL21R	ENST00000564089.5	c.-16-94A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120073 AN: 151852 Hom.: 47743 Cov.: 29

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.796 AC: 713142 AN: 895720 Hom.: 286145 AF XY: 0.801 AC XY: 364650 AN XY: 455432

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.834

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.781

GnomAD4 genome AF: 0.791 AC: 120173 AN: 151970 Hom.: 47785 Cov.: 29 AF XY: 0.799 AC XY: 59367 AN XY: 74292

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.746

Alfa AF: 0.764 Hom.: 56507

Bravo AF: 0.781

Asia WGS AF: 0.943 AC: 3277 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.030
Dann	Benign	0.25

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: rs179760; hg19: chr16-27441283;