Menu
GeneBe

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 151080 control chromosomes in the gnomAD Genomes database, including 28000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28000 hom., cov: 29)
Exomes 𝑓: 0.64 ( 44741 hom. )

Consequence

CYP21A2
NM_000500.9 splice_polypyrimidine_tract, intron

Scores

1
13

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.233

Links

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
?
GnomAd 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
CYP21A2NM_000500.9 linkuse as main transcriptc.293-13C>A splice_polypyrimidine_tract_variant, intron_variant ENST00000644719.2
CYP21A2NM_001368143.2 linkuse as main transcriptc.-126C>A 5_prime_UTR_variant 3/10
CYP21A2NM_001368144.2 linkuse as main transcriptc.-126C>A 5_prime_UTR_variant 2/9
CYP21A2NM_001128590.4 linkuse as main transcriptc.203-13C>A splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP21A2ENST00000644719.2 linkuse as main transcriptc.293-13C>A splice_polypyrimidine_tract_variant, intron_variant NM_000500.9 P1

Frequencies

GnomAD3 genomes
AF:
0.609
AC:
91969
AN:
151080
Hom.:
28000
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.637
Gnomad AMI
AF:
0.639
Gnomad AMR
AF:
0.711
Gnomad ASJ
AF:
0.636
Gnomad EAS
AF:
0.631
Gnomad SAS
AF:
0.596
Gnomad FIN
AF:
0.436
Gnomad MID
AF:
0.621
Gnomad NFE
AF:
0.592
Gnomad OTH
AF:
0.644
GnomAD3 exomes
AF:
0.637
AC:
141158
AN:
221616
Hom.:
44741
AF XY:
0.635
AC XY:
75748
AN XY:
119232
show subpopulations
Gnomad AFR exome
AF:
0.675
Gnomad AMR exome
AF:
0.739
Gnomad ASJ exome
AF:
0.659
Gnomad EAS exome
AF:
0.634
Gnomad SAS exome
AF:
0.629
Gnomad FIN exome
AF:
0.475
Gnomad NFE exome
AF:
0.630
Gnomad OTH exome
AF:
0.644
Alfa
AF:
0.561
Hom.:
9188
Bravo
AF:
0.636
TwinsUK
AF:
0.614
AC:
2275
ALSPAC
AF:
0.607
AC:
2338
ESP6500AA
AF:
0.656
AC:
2883
ESP6500EA
AF:
0.616
AC:
5296
ExAC
AF:
0.608
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, criteria provided, single submitterclinical testingPreventionGenetics, Part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Sep 23, 2014- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxFeb 15, 2019- -
Benign, criteria provided, single submitterclinical testingInvitaeNov 04, 2022- -
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabMay 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
1.6
Dann
Benign
0.44
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0018
N
LIST_S2
Benign
0.23
T
MetaRNN
Benign
0.0000017
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
P;P
PROVEAN
Benign
0.40
N
REVEL
Benign
0.034
Sift
Benign
0.31
T
Sift4G
Pathogenic
0.0
D
ClinPred
0.0018
T
GERP RS
-0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6467; hg19: chr6-32006858; COSMIC: COSV64479798; COSMIC: COSV64479798; API