4-122612712-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_021803.4(IL21):ā€‹c.487T>Cā€‹(p.Ter163ArgextTer15) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IL21
NM_021803.4 stop_lost

Scores

7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.314
Variant links:
Genes affected
IL21 (HGNC:6005): (interleukin 21) This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_021803.4 Downstream stopcodon found after 16 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL21NM_021803.4 linkuse as main transcriptc.487T>C p.Ter163ArgextTer15 stop_lost 5/5 ENST00000648588.1 NP_068575.1
IL21NM_001207006.3 linkuse as main transcriptc.*115T>C 3_prime_UTR_variant 4/4 NP_001193935.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL21ENST00000648588.1 linkuse as main transcriptc.487T>C p.Ter163ArgextTer15 stop_lost 5/5 NM_021803.4 ENSP00000497915 P1Q9HBE4-1
IL21ENST00000611104.2 linkuse as main transcriptc.*115T>C 3_prime_UTR_variant 4/41 ENSP00000477555 Q9HBE4-2
IL21ENST00000647784.1 linkuse as main transcriptn.339T>C non_coding_transcript_exon_variant 4/4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250636
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135524
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1453446
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
723782
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 25, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with IL21-related conditions. This variant is present in population databases (rs750573471, gnomAD 0.003%). This sequence change disrupts the translational stop signal of the IL21 mRNA. It is expected to extend the length of the IL21 protein by 15 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
7.9
DANN
Benign
0.50
Eigen
Benign
-0.058
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.0090
N
MutationTaster
Benign
1.0
N
Vest4
0.44
GERP RS
-6.8

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.

Other links and lift over

dbSNP: rs750573471; hg19: chr4-123533867; API