16-27446045-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_181078.3(IL21R):c.824G>A(p.Arg275Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,613,584 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_181078.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00672 AC: 1021AN: 152040Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00560 AC: 1404AN: 250642Hom.: 8 AF XY: 0.00551 AC XY: 747AN XY: 135496
GnomAD4 exome AF: 0.0101 AC: 14702AN: 1461426Hom.: 99 Cov.: 31 AF XY: 0.00986 AC XY: 7165AN XY: 727024
GnomAD4 genome AF: 0.00671 AC: 1021AN: 152158Hom.: 7 Cov.: 32 AF XY: 0.00629 AC XY: 468AN XY: 74384
ClinVar
Submissions by phenotype
not provided Benign:2
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IL21R: BP4, BS1, BS2 -
not specified Uncertain:1
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IgE responsiveness, atopic;C3554687:Cryptosporidiosis-chronic cholangitis-liver disease syndrome Uncertain:1
IL21R NM_021798.3 exon 8 p.Arg275Gln (c.824G>A): This variant has not been reported in the literature but is present in 0.9% (1254/128760) of European alleles, including 9 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/16-27457366-G-A). This variant is present in ClinVar (Variation ID: 252799). This variant amino acid Glutamine (Gln) is present in >10 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
Cryptosporidiosis-chronic cholangitis-liver disease syndrome Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at