Variant 6-32040013-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000500.9(CYP21A2):c.747C>G(p.Leu249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,424,980 control chromosomes in the GnomAD database, including 16,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2057 hom., cov: 31)

Exomes 𝑓: 0.075 ( 14195 hom. )

Consequence

CYP21A2
NM_000500.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0220

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 6-32040013-C-G is Benign according to our data. Variant chr6-32040013-C-G is described in ClinVar as [Benign]. Clinvar id is 256300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32040013-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.022 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP21A2	NM_000500.9 linkuse as main transcript	c.747C>G	p.Leu249=	synonymous_variant	7/10	ENST00000644719.2
CYP21A2	NM_001128590.4 linkuse as main transcript	c.657C>G	p.Leu219=	synonymous_variant	6/9
CYP21A2	NM_001368143.2 linkuse as main transcript	c.342C>G	p.Leu114=	synonymous_variant	7/10
CYP21A2	NM_001368144.2 linkuse as main transcript	c.342C>G	p.Leu114=	synonymous_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.747C>G	p.Leu249=	synonymous_variant	7/10		NM_000500.9	P1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

24259

AN:

145264

Hom.:

2054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.125

AC:

26859

AN:

215192

Hom.:

3468

AF XY:

0.124

AC XY:

14349

AN XY:

115746

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.0923

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.0890

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.0749

AC:

95820

AN:

1279602

Hom.:

14195

Cov.:

AF XY:

0.0793

AC XY:

50561

AN XY:

637396

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0979

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.0512

Gnomad4 OTH exome

AF:

0.0936

GnomAD4 genome

AF:

0.167

AC:

24262

AN:

145378

Hom.:

2057

Cov.:

AF XY:

0.170

AC XY:

12076

AN XY:

71008

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.0968

Hom.:

144

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 25, 2021	- -
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

-0.48

CADD

Benign

9.3

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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