rs6464
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000500.9(CYP21A2):c.138C>A(p.Pro46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 150,242 control chromosomes in the GnomAD database, including 36,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.71 ( 36743 hom., cov: 29)
Exomes 𝑓: 0.70 ( 340401 hom. )
Failed GnomAD Quality Control
Consequence
CYP21A2
NM_000500.9 synonymous
NM_000500.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.442
Genes affected
CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 6-32038560-C-A is Benign according to our data. Variant chr6-32038560-C-A is described in ClinVar as [Benign]. Clinvar id is 256287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32038560-C-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.442 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP21A2 | NM_000500.9 | c.138C>A | p.Pro46= | synonymous_variant | 1/10 | ENST00000644719.2 | |
CYP21A2 | NM_001128590.4 | c.138C>A | p.Pro46= | synonymous_variant | 1/9 | ||
CYP21A2 | NM_001368143.2 | c.-287C>A | 5_prime_UTR_variant | 1/10 | |||
CYP21A2 | NM_001368144.2 | c.-197C>A | 5_prime_UTR_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP21A2 | ENST00000644719.2 | c.138C>A | p.Pro46= | synonymous_variant | 1/10 | NM_000500.9 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.709 AC: 106472AN: 150122Hom.: 36709 Cov.: 29
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GnomAD3 exomes AF: 0.689 AC: 146582AN: 212814Hom.: 48011 AF XY: 0.685 AC XY: 79271AN XY: 115772
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.700 AC: 1010880AN: 1444304Hom.: 340401 Cov.: 96 AF XY: 0.698 AC XY: 500628AN XY: 717004
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? AF: 0.709 AC: 106560AN: 150242Hom.: 36743 Cov.: 29 AF XY: 0.708 AC XY: 51976AN XY: 73366
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at