Variant chr16-27434331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_181078.3(IL21R):c.50-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000547 in 1,571,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

IL21R
NM_181078.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-27434331-C-T is Benign according to our data. Variant chr16-27434331-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1587789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3 linkuse as main transcript	c.50-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
IL21R	ENST00000337929.8 linkuse as main transcript	c.50-16C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4 linkuse as main transcript	c.50-16C>T	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000379103	P1
IL21R	ENST00000564089.5 linkuse as main transcript	c.50-16C>T	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000456707	P1
IL21R	ENST00000697146.1 linkuse as main transcript	c.50-16C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant			ENSP00000513135

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000922

AC:

AN:

249586

Hom.:

AF XY:

0.0000889

AC XY:

AN XY:

134982

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1419100

Hom.:

Cov.:

AF XY:

0.0000452

AC XY:

AN XY:

708536

show subpopulations

Gnomad4 AFR exome

AF:

0.000368

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000118

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000193

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.50

DANN

Benign

0.58

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