8-142876322-C-T

Position:

chr8-142876322-C-T

Variant summary

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

The NM_000497.4(CYP11B1):c.873G>A(p.Ala291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 1,612,086 control chromosomes in the GnomAD database, including 3,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1078 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1924 hom. )

Consequence

CYP11B1
NM_000497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.62

Variant links:

Genes affected

CYP11B1 (HGNC:2591): (cytochrome P450 family 11 subfamily B member 1) 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 and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

CYP11B1 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=-0.81).

BP6

Variant 8-142876322-C-T is Benign according to our data. Variant chr8-142876322-C-T is described in ClinVar as [Benign]. Clinvar id is 362157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP11B1	NM_000497.4 linkuse as main transcript	c.873G>A	p.Ala291=	synonymous_variant	5/9	ENST00000292427.10	NP_000488.3
CYP11B1	NM_001026213.1 linkuse as main transcript	c.873G>A	p.Ala291=	synonymous_variant	5/8		NP_001021384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.873G>A	p.Ala291=	synonymous_variant	5/9	1	NM_000497.4	ENSP00000292427	P1	P15538-1

Frequencies

GnomAD3 genomes

AF:

0.0855

AC:

12894

AN:

150874

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.0788

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0876

GnomAD3 exomes

AF:

0.0536

AC:

13452

AN:

251052

Hom.:

705

AF XY:

0.0514

AC XY:

6971

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0418

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0775

Gnomad SAS exome

AF:

0.0754

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0368

AC:

53701

AN:

1461108

Hom.:

1924

Cov.:

AF XY:

0.0375

AC XY:

27266

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.0692

Gnomad4 SAS exome

AF:

0.0735

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.0855

AC:

12916

AN:

150978

Hom.:

1078

Cov.:

AF XY:

0.0851

AC XY:

6279

AN XY:

73824

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.0455

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.0790

Gnomad4 SAS

AF:

0.0803

Gnomad4 FIN

AF:

0.0376

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0863

Alfa

AF:

0.0624

Hom.:

296

Bravo

AF:

0.0936

Asia WGS

AF:

0.0920

AC:

317

AN:

3476

EpiCase

AF:

0.0315

EpiControl

AF:

0.0302

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 25, 2019	- -

Deficiency of steroid 11-beta-monooxygenase

Benign:2

Benign, criteria provided, single submitter	clinical testing	Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	Apr 20, 2020	- -
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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 12, 2017

- -

Glucocorticoid-remediable aldosteronism

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.091

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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