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]
Genome browser will be placed here
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 | UniProt |
---|---|---|---|---|---|---|---|
CYP21A2 | NM_000500.9 | c.293-13C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000644719.2 | |||
CYP21A2 | NM_001368143.2 | c.-126C>A | 5_prime_UTR_variant | 3/10 | |||
CYP21A2 | NM_001368144.2 | c.-126C>A | 5_prime_UTR_variant | 2/9 | |||
CYP21A2 | NM_001128590.4 | c.203-13C>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP21A2 | ENST00000644719.2 | c.293-13C>A | splice_polypyrimidine_tract_variant, intron_variant | NM_000500.9 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.609 AC: 91969AN: 151080Hom.: 28000 Cov.: 29
GnomAD3 genomes
?
AF:
AC:
91969
AN:
151080
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.637 AC: 141158AN: 221616Hom.: 44741 AF XY: 0.635 AC XY: 75748AN XY: 119232
GnomAD3 exomes
AF:
AC:
141158
AN:
221616
Hom.:
AF XY:
AC XY:
75748
AN XY:
119232
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
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
AF:
AC:
857154
AN:
1440498
Hom.:
Cov.:
74
AF XY:
AC XY:
425953
AN XY:
714448
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.609 AC: 92050AN: 151196Hom.: 28032 Cov.: 29 AF XY: 0.605 AC XY: 44652AN XY: 73832
GnomAD4 genome
?
AF:
AC:
92050
AN:
151196
Hom.:
Cov.:
29
AF XY:
AC XY:
44652
AN XY:
73832
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2275
ALSPAC
AF:
AC:
2338
ESP6500AA
AF:
AC:
2883
ESP6500EA
AF:
AC:
5296
ExAC
?
AF:
AC:
73208
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 23, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | 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
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at