16-27445292-G-C

Variant summary

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

The NM_181078.3(IL21R):c.785+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,578,392 control chromosomes in the GnomAD database, including 74,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9550 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65201 hom. )

Consequence

IL21R
NM_181078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.31

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:

LOC124903668 (HGNC:):

LOC124903668 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=-0.91).

BP6

Variant 16-27445292-G-C is Benign according to our data. Variant chr16-27445292-G-C is described in ClinVar as [Benign]. Clinvar id is 1170239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-27445292-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3 linkuse as main transcript	c.785+16G>C		intron_variant		ENST00000337929.8
LOC124903668	XR_007065031.1 linkuse as main transcript	n.44C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8 linkuse as main transcript	c.785+16G>C		intron_variant		1	NM_181078.3	P1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52146

AN:

151846

Hom.:

9515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.324

GnomAD3 exomes

AF:

0.275

AC:

68071

AN:

247774

Hom.:

10462

AF XY:

0.266

AC XY:

35639

AN XY:

133950

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.0954

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.295

AC:

420978

AN:

1426428

Hom.:

65201

Cov.:

AF XY:

0.289

AC XY:

205849

AN XY:

711470

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.344

AC:

52217

AN:

151964

Hom.:

9550

Cov.:

AF XY:

0.344

AC XY:

25517

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.241

Hom.:

882

Bravo

AF:

0.346

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.35

Dann

Benign

0.69

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