Variant rs6458 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000500.9(CYP21A2):c.738+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,603,274 control chromosomes in the GnomAD database, including 12,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1808 hom., cov: 31)

Exomes 𝑓: 0.11 ( 10413 hom. )

Consequence

CYP21A2
NM_000500.9 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57

Variant links:

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]

CYP21A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-32039847-A-G is Benign according to our data. Variant chr6-32039847-A-G is described in ClinVar as [Benign]. Clinvar id is 256298.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32039847-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CYP21A2	NM_000500.9 linkuse as main transcript	c.738+12A>G	intron_variant	ENST00000644719.2	NP_000491.4
CYP21A2	NM_001128590.4 linkuse as main transcript	c.648+12A>G	intron_variant		NP_001122062.3
CYP21A2	NM_001368143.2 linkuse as main transcript	c.333+12A>G	intron_variant		NP_001355072.1
CYP21A2	NM_001368144.2 linkuse as main transcript	c.333+12A>G	intron_variant		NP_001355073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.738+12A>G		intron_variant			NM_000500.9	ENSP00000496625	P1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22251

AN:

151392

Hom.:

1800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0700

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.131

AC:

31911

AN:

242802

Hom.:

2351

AF XY:

0.135

AC XY:

17711

AN XY:

131182

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.0973

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.0718

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.115

AC:

166679

AN:

1451760

Hom.:

10413

Cov.:

AF XY:

0.119

AC XY:

85600

AN XY:

721856

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.0752

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.147

AC:

22282

AN:

151514

Hom.:

1808

Cov.:

AF XY:

0.148

AC XY:

10926

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.0700

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.0739

Hom.:

134

Bravo

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.39

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over