rs3802230

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000498.3(CYP11B2):c.*532G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 169,460 control chromosomes in the GnomAD database, including 33,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30919 hom., cov: 31)

Exomes 𝑓: 0.55 ( 2771 hom. )

Consequence

CYP11B2
NM_000498.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.444

Publications

19 publications found

Variant links:

Genes affected

CYP11B2 (HGNC:2592): (cytochrome P450 family 11 subfamily B 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 mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency. [provided by RefSeq, Jul 2008]

CYP11B2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-142911448-C-A is Benign according to our data. Variant chr8-142911448-C-A is described in ClinVar as Benign. ClinVar VariationId is 362184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11B2	NM_000498.3 link	c.*532G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000323110.2	NP_000489.3	P19099

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP11B2	ENST00000323110.2 link	c.*532G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000498.3	ENSP00000325822.2		P19099
GML	ENST00000522728.5 link	c.182-2515C>A		intron_variant	Intron 3 of 4	3		ENSP00000430799.1		E5RI31

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

94628

AN:

151922

Hom.:

30897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.626

GnomAD4 exome

AF:

0.549

AC:

9556

AN:

17420

Hom.:

2771

Cov.:

AF XY:

0.554

AC XY:

4909

AN XY:

8866

show subpopulations

African (AFR)

AF:

0.861

AC:

434

AN:

504

American (AMR)

AF:

0.546

AC:

1564

AN:

2866

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

159

AN:

276

East Asian (EAS)

AF:

0.354

AC:

404

AN:

1140

South Asian (SAS)

AF:

0.609

AC:

997

AN:

1638

European-Finnish (FIN)

AF:

0.608

AC:

186

AN:

306

Middle Eastern (MID)

AF:

0.591

AC:

AN:

European-Non Finnish (NFE)

AF:

0.542

AC:

5340

AN:

9850

Other (OTH)

AF:

0.560

AC:

446

AN:

796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

209

418

626

835

1044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.623

AC:

94690

AN:

152040

Hom.:

30919

Cov.:

AF XY:

0.621

AC XY:

46167

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.828

AC:

34369

AN:

41514

American (AMR)

AF:

0.562

AC:

8578

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2133

AN:

3472

East Asian (EAS)

AF:

0.339

AC:

1749

AN:

5162

South Asian (SAS)

AF:

0.564

AC:

2711

AN:

4806

European-Finnish (FIN)

AF:

0.562

AC:

5937

AN:

10556

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.547

AC:

37196

AN:

67938

Other (OTH)

AF:

0.621

AC:

1312

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1692

3384

5075

6767

8459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.607

Hom.:

27521

Bravo

AF:

0.629

Asia WGS

AF:

0.444

AC:

1548

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Corticosterone methyloxidase type 2 deficiency

Benign:1

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. -

Corticosterone 18-monooxygenase deficiency

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.90

CADD

Benign

4.0

(source)

DANN

Benign

0.46

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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