Variant 6-32038820-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000500.9(CYP21A2):c.292+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,378,688 control chromosomes in the GnomAD database, including 343,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 38407 hom., cov: 28)

Exomes 𝑓: 0.71 ( 305415 hom. )

Consequence

CYP21A2
NM_000500.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.82

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-32038820-C-T is Benign according to our data. Variant chr6-32038820-C-T is described in ClinVar as [Benign]. Clinvar id is 256289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32038820-C-T is described in Lovd as [Benign]. Variant chr6-32038820-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CYP21A2	NM_000500.9 linkuse as main transcript	c.292+9C>T	intron_variant	ENST00000644719.2	NP_000491.4
CYP21A2	NM_001128590.4 linkuse as main transcript	c.202+196C>T	intron_variant		NP_001122062.3
CYP21A2	NM_001368143.2 linkuse as main transcript	c.-133+9C>T	intron_variant		NP_001355072.1
CYP21A2	NM_001368144.2 linkuse as main transcript	c.-133+196C>T	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.292+9C>T		intron_variant			NM_000500.9	ENSP00000496625	P1

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

107500

AN:

150210

Hom.:

38353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.666

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.763

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.793

Gnomad MID

AF:

0.694

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.732

GnomAD3 exomes

AF:

0.737

AC:

157800

AN:

214146

Hom.:

58091

AF XY:

0.733

AC XY:

84877

AN XY:

115832

show subpopulations

Gnomad AFR exome

AF:

0.660

Gnomad AMR exome

AF:

0.836

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.685

Gnomad SAS exome

AF:

0.707

Gnomad FIN exome

AF:

0.785

Gnomad NFE exome

AF:

0.722

Gnomad OTH exome

AF:

0.728

GnomAD4 exome

AF:

0.707

AC:

868177

AN:

1228364

Hom.:

305415

Cov.:

AF XY:

0.708

AC XY:

437559

AN XY:

618032

show subpopulations

Gnomad4 AFR exome

AF:

0.661

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.741

Gnomad4 EAS exome

AF:

0.677

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.778

Gnomad4 NFE exome

AF:

0.701

Gnomad4 OTH exome

AF:

0.703

GnomAD4 genome

AF:

0.716

AC:

107613

AN:

150324

Hom.:

38407

Cov.:

AF XY:

0.717

AC XY:

52661

AN XY:

73464

show subpopulations

Gnomad4 AFR

AF:

0.666

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.763

Gnomad4 EAS

AF:

0.685

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.793

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.735

Alfa

AF:

0.709

Hom.:

9402

Bravo

AF:

0.717

Asia WGS

AF:

0.745

AC:

2592

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.087

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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