Variant rs3093369 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_181078.3(IL21R):c.531A>G(p.Ser177Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,538,416 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 33 hom. )

Consequence

IL21R
NM_181078.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.66

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-27444565-A-G is Benign according to our data. Variant chr16-27444565-A-G is described in ClinVar as [Benign]. Clinvar id is 473944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.66 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1640/152282) while in subpopulation AFR AF= 0.0373 (1549/41534). AF 95% confidence interval is 0.0357. There are 46 homozygotes in gnomad4. There are 776 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.531A>G	p.Ser177Ser	synonymous_variant	6/9	ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 link	c.531A>G	p.Ser177Ser	synonymous_variant	6/9	1	NM_181078.3	ENSP00000338010.3		Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1621

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00297

AC:

568

AN:

191300

Hom.:

AF XY:

0.00200

AC XY:

207

AN XY:

103454

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00119

AC:

1643

AN:

1386134

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

746

AN XY:

685756

show subpopulations

Gnomad4 AFR exome

AF:

0.0401

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.000524

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000216

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00314

GnomAD4 genome

AF:

0.0108

AC:

1640

AN:

152282

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0373

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00872

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00491

AC:

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.95

DANN

Benign

0.66

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