rs6467
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000500.9(CYP21A2):c.293-13C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,196 control chromosomes in the GnomAD database, including 28,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.61 ( 28032 hom., cov: 29)
Exomes 𝑓: 0.60 ( 254518 hom. )
Failed GnomAD Quality Control
Consequence
CYP21A2
NM_000500.9 splice_polypyrimidine_tract, intron
NM_000500.9 splice_polypyrimidine_tract, intron
Scores
1
13
Clinical Significance
Conservation
PhyloP100: -0.233
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=1.7294652E-6).
BP6
Variant 6-32039081-C-A is Benign according to our data. Variant chr6-32039081-C-A is described in ClinVar as [Benign]. Clinvar id is 196278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32039081-C-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP21A2 | NM_000500.9 | c.293-13C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000644719.2 | NP_000491.4 | |||
CYP21A2 | NM_001368143.2 | c.-126C>A | 5_prime_UTR_variant | 3/10 | NP_001355072.1 | |||
CYP21A2 | NM_001368144.2 | c.-126C>A | 5_prime_UTR_variant | 2/9 | NP_001355073.1 | |||
CYP21A2 | NM_001128590.4 | c.203-13C>A | splice_polypyrimidine_tract_variant, intron_variant | NP_001122062.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP21A2 | ENST00000644719.2 | c.293-13C>A | splice_polypyrimidine_tract_variant, intron_variant | NM_000500.9 | ENSP00000496625 | P1 |
Frequencies
GnomAD3 genomes AF: 0.609 AC: 91969AN: 151080Hom.: 28000 Cov.: 29
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GnomAD3 exomes AF: 0.637 AC: 141158AN: 221616Hom.: 44741 AF XY: 0.635 AC XY: 75748AN XY: 119232
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.595 AC: 857154AN: 1440498Hom.: 254518 Cov.: 74 AF XY: 0.596 AC XY: 425953AN XY: 714448
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.609 AC: 92050AN: 151196Hom.: 28032 Cov.: 29 AF XY: 0.605 AC XY: 44652AN XY: 73832
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 23, 2014 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 2019 | - - |
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 12, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Pathogenic
D
ClinPred
T
GERP RS
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