chr16-27430091-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_181078.3(IL21R):c.20C>G(p.Ala7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,605,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7T) has been classified as Likely benign.
Frequency
Consequence
NM_181078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL21R | ENST00000337929.8 | c.20C>G | p.Ala7Gly | missense_variant | Exon 2 of 9 | 1 | NM_181078.3 | ENSP00000338010.3 | ||
IL21R | ENST00000395754.4 | c.20C>G | p.Ala7Gly | missense_variant | Exon 2 of 9 | 1 | ENSP00000379103.4 | |||
IL21R | ENST00000564089.5 | c.20C>G | p.Ala7Gly | missense_variant | Exon 3 of 10 | 5 | ENSP00000456707.1 | |||
IL21R | ENST00000697146.1 | n.20C>G | non_coding_transcript_exon_variant | Exon 1 of 7 | ENSP00000513135.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239416Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130890
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1453028Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 723266
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152362Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74508
ClinVar
Submissions by phenotype
Cryptosporidiosis-chronic cholangitis-liver disease syndrome Uncertain:1
This variant has not been reported in the literature in individuals with IL21R-related conditions. This variant is present in population databases (rs559469718, ExAC 0.009%). This sequence change replaces alanine with glycine at codon 7 of the IL21R protein (p.Ala7Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. -
Inborn genetic diseases Uncertain:1
The c.86C>G (p.A29G) alteration is located in exon 3 (coding exon 2) of the IL21R gene. This alteration results from a C to G substitution at nucleotide position 86, causing the alanine (A) at amino acid position 29 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at