chr16-27429962-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.924

Variant links:

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]

IL21R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.-16-94A>G		intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL21R	ENST00000337929.8 link	c.-16-94A>G	intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4 link	c.-16-94A>G	intron_variant	Intron 1 of 8	1		ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5 link	c.-16-94A>G	intron_variant	Intron 2 of 9	5		ENSP00000456707.1	Q9HBE5
IL21R	ENST00000697146.1 link	n.-110A>G	upstream_gene_variant				ENSP00000513135.1	A0A8V8TL34

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120073

AN:

151852

Hom.:

47743

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.799

AC XY:

59367

AN XY:

74292

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over