rs34570566

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000497.4(CYP11B1):c.873G>A(p.Ala291Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 1,612,086 control chromosomes in the GnomAD database, including 3,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1078 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1924 hom. )

Consequence

CYP11B1
NM_000497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.62

Publications

9 publications found

Variant links:

Genes affected

CYP11B1 (HGNC:2591): (cytochrome P450 family 11 subfamily B member 1) 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 mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

CYP11B1 links:

GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GML links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-142876322-C-T is Benign according to our data. Variant chr8-142876322-C-T is described in ClinVar as Benign. ClinVar VariationId is 362157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11B1	NM_000497.4 link	c.873G>A	p.Ala291Ala	synonymous_variant	Exon 5 of 9	ENST00000292427.10	NP_000488.3	P15538-1Q8TDD0
CYP11B1	NM_001026213.1 link	c.873G>A	p.Ala291Ala	synonymous_variant	Exon 5 of 8		NP_001021384.1	P15538-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP11B1	ENST00000292427.10 link	c.873G>A	p.Ala291Ala	synonymous_variant	Exon 5 of 9	1	NM_000497.4	ENSP00000292427.5		P15538-1

Frequencies

GnomAD3 genomes

AF:

0.0855

AC:

12894

AN:

150874

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.0788

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0876

GnomAD2 exomes

AF:

0.0536

AC:

13452

AN:

251052

AF XY:

0.0514

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0418

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0775

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0368

AC:

53701

AN:

1461108

Hom.:

1924

Cov.:

AF XY:

0.0375

AC XY:

27266

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.226

AC:

7440

AN:

32948

American (AMR)

AF:

0.0424

AC:

1893

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

1348

AN:

26134

East Asian (EAS)

AF:

0.0692

AC:

2747

AN:

39698

South Asian (SAS)

AF:

0.0735

AC:

6343

AN:

86252

European-Finnish (FIN)

AF:

0.0383

AC:

2044

AN:

53418

Middle Eastern (MID)

AF:

0.0963

AC:

555

AN:

5762

European-Non Finnish (NFE)

AF:

0.0254

AC:

28290

AN:

1111942

Other (OTH)

AF:

0.0504

AC:

3041

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3276

6551

9827

13102

16378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1236

2472

3708

4944

6180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0855

AC:

12916

AN:

150978

Hom.:

1078

Cov.:

AF XY:

0.0851

AC XY:

6279

AN XY:

73824

show subpopulations

African (AFR)

AF:

0.221

AC:

8918

AN:

40312

American (AMR)

AF:

0.0455

AC:

693

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3470

East Asian (EAS)

AF:

0.0790

AC:

409

AN:

5180

South Asian (SAS)

AF:

0.0803

AC:

387

AN:

4822

European-Finnish (FIN)

AF:

0.0376

AC:

399

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0258

AC:

1754

AN:

68018

Other (OTH)

AF:

0.0863

AC:

182

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

566

1132

1699

2265

2831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0638

Hom.:

311

Bravo

AF:

0.0936

Asia WGS

AF:

0.0920

AC:

317

AN:

3476

EpiCase

AF:

0.0315

EpiControl

AF:

0.0302

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deficiency of steroid 11-beta-monooxygenase

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 20, 2020

Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glucocorticoid-remediable aldosteronism

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.091

(source)

DANN

Benign

0.78

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over