16-27430098-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_181078.3(IL21R):c.27G>T(p.Leu9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,452,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_181078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL21R | NM_181078.3 | c.27G>T | p.Leu9Phe | missense_variant | 2/9 | ENST00000337929.8 | NP_851564.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL21R | ENST00000337929.8 | c.27G>T | p.Leu9Phe | missense_variant | 2/9 | 1 | NM_181078.3 | ENSP00000338010 | P1 | |
IL21R | ENST00000395754.4 | c.27G>T | p.Leu9Phe | missense_variant | 2/9 | 1 | ENSP00000379103 | P1 | ||
IL21R | ENST00000564089.5 | c.27G>T | p.Leu9Phe | missense_variant | 3/10 | 5 | ENSP00000456707 | P1 | ||
IL21R | ENST00000697146.1 | c.27G>T | p.Leu9Phe | missense_variant, NMD_transcript_variant | 1/7 | ENSP00000513135 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000167 AC: 4AN: 239092Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130790
GnomAD4 exome AF: 0.00000757 AC: 11AN: 1452802Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 723166
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cryptosporidiosis-chronic cholangitis-liver disease syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 24, 2021 | This sequence change replaces leucine with phenylalanine at codon 9 of the IL21R protein (p.Leu9Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs758665836, ExAC 0.002%). This variant has not been reported in the literature in individuals with IL21R-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at