chr6-32038342-A-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The ENST00000486063.5(CYP21A2):n.3A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,541,254 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
ENST00000486063.5 non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP21A2 | ENST00000466779.5 | n.-81A>C | non_coding_transcript_exon_variant | Exon 1 of 6 | 5 | ENSP00000417321.1 | ||||
CYP21A2 | ENST00000486063.5 | n.3A>C | non_coding_transcript_exon_variant | Exon 1 of 8 | 3 | |||||
CYP21A2 | ENST00000466779.5 | n.-81A>C | 5_prime_UTR_variant | Exon 1 of 6 | 5 | ENSP00000417321.1 |
Frequencies
GnomAD3 genomes AF: 0.0124 AC: 1889AN: 152110Hom.: 31 Cov.: 32
GnomAD4 exome AF: 0.0146 AC: 20311AN: 1389026Hom.: 245 Cov.: 30 AF XY: 0.0140 AC XY: 9563AN XY: 685394
GnomAD4 genome AF: 0.0124 AC: 1889AN: 152228Hom.: 31 Cov.: 32 AF XY: 0.0125 AC XY: 931AN XY: 74438
ClinVar
Submissions by phenotype
CYP21A2-related disorder Uncertain:1
The CYP21A2 c.-81A>C variant is located in the 5' untranslated region. To our knowledge, this variant has not been reported in the literature. Its minor allele frequency is up to ~2.5% in a subpopulation of the gnomAD database. However, this population frequency data may not be reliable since the variant is located within a highly homologous sequence region, and current next-generation sequencing technology may not accurately assign sequencing reads from the gene and pseudogene (Mandelker et al. 2016. PubMed ID: 27228465). Due to limited functional and genetic evidence, the clinical significance of the c.-81A>C variant is currently uncertain. Of note, promoter variants in CYP21A2 have been reported to reduce transcriptional activities and therefore could be associated with mild disease (Zhang et al. 2009. PubMed ID: 18702679; Araújo et al. 2007. PubMed ID: 17666484). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at