8-142911899-C-T

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.*81G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,599,268 control chromosomes in the GnomAD database, including 59,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3912 hom., cov: 31)

Exomes 𝑓: 0.27 ( 55203 hom. )

Consequence

CYP11B2
NM_000498.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0500

Publications

17 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=-0.8).

BP6

Variant 8-142911899-C-T is Benign according to our data. Variant chr8-142911899-C-T is described in ClinVar as Benign. ClinVar VariationId is 362191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11B2	NM_000498.3 link	c.*81G>A		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.*81G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_000498.3	ENSP00000325822.2		P19099
GML	ENST00000522728.5 link	c.182-2064C>T		intron_variant	Intron 3 of 4	3		ENSP00000430799.1		E5RI31

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30343

AN:

151388

Hom.:

3917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.0601

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.196

GnomAD4 exome

AF:

0.269

AC:

389110

AN:

1447764

Hom.:

55203

Cov.:

AF XY:

0.267

AC XY:

192425

AN XY:

719620

show subpopulations

African (AFR)

AF:

0.0457

AC:

1520

AN:

33248

American (AMR)

AF:

0.138

AC:

5965

AN:

43098

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

6323

AN:

25680

East Asian (EAS)

AF:

0.0608

AC:

2395

AN:

39384

South Asian (SAS)

AF:

0.189

AC:

16091

AN:

85132

European-Finnish (FIN)

AF:

0.262

AC:

13772

AN:

52576

Middle Eastern (MID)

AF:

0.201

AC:

1064

AN:

5292

European-Non Finnish (NFE)

AF:

0.297

AC:

327219

AN:

1103556

Other (OTH)

AF:

0.247

AC:

14761

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

14605

29209

43814

58418

73023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10540

21080

31620

42160

52700

<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:

0.200

AC:

30322

AN:

151504

Hom.:

3912

Cov.:

AF XY:

0.196

AC XY:

14477

AN XY:

74018

show subpopulations

African (AFR)

AF:

0.0526

AC:

2172

AN:

41262

American (AMR)

AF:

0.182

AC:

2779

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

854

AN:

3466

East Asian (EAS)

AF:

0.0605

AC:

306

AN:

5062

South Asian (SAS)

AF:

0.186

AC:

894

AN:

4798

European-Finnish (FIN)

AF:

0.265

AC:

2798

AN:

10562

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.293

AC:

19874

AN:

67798

Other (OTH)

AF:

0.193

AC:

405

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1161

2323

3484

4646

5807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.236

Hom.:

572

Bravo

AF:

0.188

Asia WGS

AF:

0.134

AC:

465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Corticosterone methyloxidase type 2 deficiency

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2021

Genome-Nilou Lab

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

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.42

PhyloP100

0.050

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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