Variant rs6442 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.939+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,609,538 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0076 ( 333 hom. )

Consequence

CYP21A2
NM_000500.9 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.61

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=-0.83).

BP6

Variant 6-32040216-G-C is Benign according to our data. Variant chr6-32040216-G-C is described in ClinVar as [Benign]. Clinvar id is 256303.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32040216-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CYP21A2	NM_000500.9 linkuse as main transcript	c.939+11G>C	intron_variant	ENST00000644719.2
CYP21A2	NM_001128590.4 linkuse as main transcript	c.849+11G>C	intron_variant
CYP21A2	NM_001368143.2 linkuse as main transcript	c.534+11G>C	intron_variant
CYP21A2	NM_001368144.2 linkuse as main transcript	c.534+11G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.939+11G>C		intron_variant			NM_000500.9	P1

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1259

AN:

150870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00912

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.0909

Gnomad SAS

AF:

0.00608

Gnomad FIN

AF:

0.0259

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00400

Gnomad OTH

AF:

0.00727

GnomAD3 exomes

AF:

0.0144

AC:

3548

AN:

246188

Hom.:

AF XY:

0.0131

AC XY:

1756

AN XY:

134194

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.0209

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.0896

Gnomad SAS exome

AF:

0.00569

Gnomad FIN exome

AF:

0.0226

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.00858

GnomAD4 exome

AF:

0.00758

AC:

11054

AN:

1458554

Hom.:

333

Cov.:

AF XY:

0.00748

AC XY:

5425

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.000881

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.00463

Gnomad4 FIN exome

AF:

0.0199

Gnomad4 NFE exome

AF:

0.00373

Gnomad4 OTH exome

AF:

0.00790

GnomAD4 genome

AF:

0.00833

AC:

1257

AN:

150984

Hom.:

Cov.:

AF XY:

0.00949

AC XY:

700

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00904

Gnomad4 ASJ

AF:

0.000868

Gnomad4 EAS

AF:

0.0915

Gnomad4 SAS

AF:

0.00587

Gnomad4 FIN

AF:

0.0259

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00720

Alfa

AF:

0.00525

Hom.:

Bravo

AF:

0.00731

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

-0.83

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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