Variant 6-32038437-CCTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000500.9(CYP21A2):c.29_31del(p.Leu10del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,604 control chromosomes in the GnomAD database, including 6,037 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6037 hom., cov: 24)

Exomes 𝑓: 0.30 ( 66363 hom. )

Failed GnomAD Quality Control

Consequence

CYP21A2
NM_000500.9 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.46

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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000500.9

BP6

Variant 6-32038437-CCTG-C is Benign according to our data. Variant chr6-32038437-CCTG-C is described in ClinVar as [Benign]. Clinvar id is 93160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32038437-CCTG-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP21A2	NM_000500.9 linkuse as main transcript	c.29_31del	p.Leu10del	inframe_deletion	1/10	ENST00000644719.2
CYP21A2	NM_001128590.4 linkuse as main transcript	c.29_31del	p.Leu10del	inframe_deletion	1/9
CYP21A2	NM_001368143.2 linkuse as main transcript	c.-396_-394del		5_prime_UTR_variant	1/10
CYP21A2	NM_001368144.2 linkuse as main transcript	c.-306_-304del		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.29_31del	p.Leu10del	inframe_deletion	1/10		NM_000500.9	P1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38005

AN:

151486

Hom.:

6030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.340

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.309

AC:

48291

AN:

156350

Hom.:

8560

AF XY:

0.302

AC XY:

25385

AN XY:

84000

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.299

AC:

419054

AN:

1401396

Hom.:

66363

AF XY:

0.299

AC XY:

207021

AN XY:

691912

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.251

AC:

38018

AN:

151604

Hom.:

6037

Cov.:

AF XY:

0.254

AC XY:

18835

AN XY:

74048

show subpopulations

Gnomad4 AFR

AF:

0.0651

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.228

Hom.:

952

Bravo

AF:

0.247

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 21, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 18, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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