8-142911448-C-A

Position:

chr8-142911448-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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 id 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/exons	MANE	Protein	UniProt
CYP11B2	NM_000498.3 linkuse as main transcript	c.*532G>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.*532G>T		3_prime_UTR_variant	9/9	1	NM_000498.3	ENSP00000325822	P1
GML	ENST00000522728.5 linkuse as main transcript	c.182-2515C>A		intron_variant		3		ENSP00000430799

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

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.576

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.609

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.623

AC:

94690

AN:

152040

Hom.:

30919

Cov.:

AF XY:

0.621

AC XY:

46167

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.828

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.564

Gnomad4 FIN

AF:

0.562

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.621

Alfa

AF:

0.582

Hom.:

9256

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

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

-0.90

CADD

Benign

4.0

DANN

Benign

0.46

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