Variant chr8-142911443-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000498.3(CYP11B2):c.*537C>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 0.062 in 170,354 control chromosomes in the GnomAD database, including 1,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 940 hom., cov: 32)

Exomes 𝑓: 0.060 ( 110 hom. )

Consequence

CYP11B2
NM_000498.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 8-142911443-G-A is Benign according to our data. Variant chr8-142911443-G-A is described in ClinVar as [Benign]. Clinvar id is 362183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP11B2	NM_000498.3 linkuse as main transcript	c.*537C>T		3_prime_UTR_variant	9/9	ENST00000323110.2	NP_000489.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11B2	ENST00000323110.2 linkuse as main transcript	c.*537C>T		3_prime_UTR_variant	9/9	1	NM_000498.3	ENSP00000325822	P1
GML	ENST00000522728.5 linkuse as main transcript	c.182-2520G>A		intron_variant		3		ENSP00000430799

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9411

AN:

152080

Hom.:

930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0660

GnomAD4 exome

AF:

0.0605

AC:

1098

AN:

18156

Hom.:

110

Cov.:

AF XY:

0.0637

AC XY:

585

AN XY:

9180

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.0621

AC:

9459

AN:

152198

Hom.:

940

Cov.:

AF XY:

0.0695

AC XY:

5171

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0535

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.502

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0654

Asia WGS

AF:

0.283

AC:

982

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Glucocorticoid-remediable aldosteronism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

DANN

Benign

0.35

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