rs4541

chr8-142875277-G-Achr8-142875277-G-Cchr8-142875277-G-T

Variant summary

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

The NM_000497.4(CYP11B1):c.1157C>T(p.Ala386Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 1,603,440 control chromosomes in the GnomAD database, including 6,424 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A386E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.054 ( 723 hom., cov: 33)

Exomes 𝑓: 0.040 ( 5701 hom. )

Consequence

CYP11B1
NM_000497.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.420

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053716004).

BP6

Variant 8-142875277-G-A is Benign according to our data. Variant chr8-142875277-G-A is described in ClinVar as [Benign]. Clinvar id is 362149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-142875277-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11B1	NM_000497.4 linkuse as main transcript	c.1157C>T	p.Ala386Val	missense_variant	7/9	ENST00000292427.10
CYP11B1	NM_001026213.1 linkuse as main transcript	c.1157C>T	p.Ala386Val	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.1157C>T	p.Ala386Val	missense_variant	7/9	1	NM_000497.4	P1	P15538-1

Frequencies

GnomAD3 genomes

AF:

0.0537

AC:

8110

AN:

151134

Hom.:

719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0582

GnomAD3 exomes

AF:

0.0784

AC:

19408

AN:

247626

Hom.:

2302

AF XY:

0.0764

AC XY:

10240

AN XY:

134016

show subpopulations

Gnomad AFR exome

AF:

0.0418

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0547

GnomAD4 exome

AF:

0.0396

AC:

57472

AN:

1452188

Hom.:

5701

Cov.:

AF XY:

0.0421

AC XY:

30458

AN XY:

722634

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.0237

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0517

GnomAD4 genome

AF:

0.0537

AC:

8121

AN:

151252

Hom.:

723

Cov.:

AF XY:

0.0593

AC XY:

4388

AN XY:

73966

show subpopulations

Gnomad4 AFR

AF:

0.0443

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0309

Gnomad4 EAS

AF:

0.430

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0595

Alfa

AF:

0.0172

Hom.:

Bravo

AF:

0.0588

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.0390

AC:

172

ESP6500EA

AF:

0.0170

AC:

146

ExAC

AF:

0.0765

AC:

9291

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Glucocorticoid-remediable aldosteronism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

Cadd

Benign

8.8

Dann

Benign

0.75

DEOGEN2

Benign

0.0083

T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00087

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

2.0

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.043, 0.049

MPC

0.084

ClinPred

0.0014

GERP RS

1.9

Varity_R

0.070

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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