NM_000498.3:c.504C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000498.3(CYP11B2):c.504C>T(p.Phe168Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,612,206 control chromosomes in the GnomAD database, including 157,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12172 hom., cov: 31)

Exomes 𝑓: 0.44 ( 144854 hom. )

Consequence

CYP11B2
NM_000498.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.58

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 8-142915137-G-A is Benign according to our data. Variant chr8-142915137-G-A is described in ClinVar as [Benign]. Clinvar id is 362221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-142915137-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11B2	NM_000498.3 link	c.504C>T	p.Phe168Phe	synonymous_variant	Exon 3 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.504C>T	p.Phe168Phe	synonymous_variant	Exon 3 of 9	1	NM_000498.3	ENSP00000325822.2		P19099
GML	ENST00000522728.5 link	c.264+1092G>A		intron_variant	Intron 4 of 4	3		ENSP00000430799.1		E5RI31

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58465

AN:

151792

Hom.:

12166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.418

GnomAD3 exomes

AF:

0.424

AC:

105583

AN:

248894

Hom.:

22865

AF XY:

0.431

AC XY:

58038

AN XY:

134608

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.292

Gnomad SAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.443

AC:

646392

AN:

1460298

Hom.:

144854

Cov.:

AF XY:

0.443

AC XY:

322145

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.498

Gnomad4 NFE exome

AF:

0.450

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.385

AC:

58497

AN:

151908

Hom.:

12172

Cov.:

AF XY:

0.390

AC XY:

28956

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.429

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.419

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.427

Hom.:

5859

Bravo

AF:

0.375

Asia WGS

AF:

0.314

AC:

1093

AN:

3476

EpiCase

AF:

0.459

EpiControl

AF:

0.459

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Phe168Phe in exon 3 of CYP11B2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 49.56% (3052/6158) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs4546). -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 02, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Corticosterone methyloxidase type 2 deficiency

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. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Corticosterone methyl oxidase type II deficiency

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

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

-0.64

CADD

Benign

7.8

DANN

Benign

0.75

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

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