rs779790998
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_181078.3(IL21R):c.495C>A(p.Asp165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 1,611,240 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 | UniProt |
---|---|---|---|---|---|---|---|
IL21R | NM_181078.3 | c.495C>A | p.Asp165Glu | missense_variant | 5/9 | ENST00000337929.8 | |
LOC124903668 | XR_007065031.1 | n.141G>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL21R | ENST00000337929.8 | c.495C>A | p.Asp165Glu | missense_variant | 5/9 | 1 | NM_181078.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000523 AC: 13AN: 248372Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134186
GnomAD4 exome AF: 0.0000672 AC: 98AN: 1459026Hom.: 0 Cov.: 31 AF XY: 0.0000689 AC XY: 50AN XY: 725744
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74410
ClinVar
Submissions by phenotype
Cryptosporidiosis-chronic cholangitis-liver disease syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 165 of the IL21R protein (p.Asp165Glu). This variant is present in population databases (rs779790998, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IL21R-related conditions. ClinVar contains an entry for this variant (Variation ID: 540992). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.561C>A (p.D187E) alteration is located in exon 6 (coding exon 5) of the IL21R gene. This alteration results from a C to A substitution at nucleotide position 561, causing the aspartic acid (D) at amino acid position 187 to be replaced by a glutamic acid (E). 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