4-122612712-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_021803.4(IL21):āc.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
NM_021803.4 stop_lost
Scores
7
Clinical Significance
Conservation
PhyloP100: -0.314
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]
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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 |
---|---|---|---|---|---|---|---|---|
IL21 | NM_021803.4 | c.487T>C | p.Ter163ArgextTer15 | stop_lost | 5/5 | ENST00000648588.1 | NP_068575.1 | |
IL21 | NM_001207006.3 | c.*115T>C | 3_prime_UTR_variant | 4/4 | NP_001193935.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL21 | ENST00000648588.1 | c.487T>C | p.Ter163ArgextTer15 | stop_lost | 5/5 | NM_021803.4 | ENSP00000497915 | P1 | ||
IL21 | ENST00000611104.2 | c.*115T>C | 3_prime_UTR_variant | 4/4 | 1 | ENSP00000477555 | ||||
IL21 | ENST00000647784.1 | n.339T>C | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250636Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135524
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1453446Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 723782
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 25, 2022 | In 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
N
Vest4
0.44
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at