rs4534

Positions:

chr8-142879686-C-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.128G>A(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,614,192 control chromosomes in the GnomAD database, including 6,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 740 hom., cov: 31)

Exomes 𝑓: 0.042 ( 6022 hom. )

Consequence

CYP11B1
NM_000497.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.228

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:

CYP11B1 (HGNC:):

CYP11B1 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=1.160652E-4).

BP6

Variant 8-142879686-C-T is Benign according to our data. Variant chr8-142879686-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 362170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 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.128G>A	p.Arg43Gln	missense_variant	1/9	ENST00000292427.10	NP_000488.3	P15538-1Q8TDD0
CYP11B1	NM_001026213.1 linkuse as main transcript	c.128G>A	p.Arg43Gln	missense_variant	1/8		NP_001021384.1	P15538-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.128G>A	p.Arg43Gln	missense_variant	1/9	1	NM_000497.4	ENSP00000292427.5		P15538-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7260

AN:

152194

Hom.:

736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0501

GnomAD3 exomes

AF:

0.0845

AC:

21242

AN:

251402

Hom.:

2690

AF XY:

0.0825

AC XY:

11216

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0567

GnomAD4 exome

AF:

0.0422

AC:

61749

AN:

1461880

Hom.:

6022

Cov.:

AF XY:

0.0448

AC XY:

32556

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.0250

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0554

GnomAD4 genome

AF:

0.0478

AC:

7274

AN:

152312

Hom.:

740

Cov.:

AF XY:

0.0539

AC XY:

4013

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0262

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0515

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0507

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.0232

AC:

102

ESP6500EA

AF:

0.0197

AC:

169

ExAC

AF:

0.0803

AC:

9754

Asia WGS

AF:

0.262

AC:

909

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0158

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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	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. -
Benign, criteria provided, single submitter	clinical testing	Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	Apr 17, 2020	- -

not provided

Benign:2

Likely 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	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Dec 10, 2021

- -

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). 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.022

DANN

Benign

0.69

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.18

T;T;T

MetaRNN

Benign

0.00012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

N;N;.

PrimateAI

Benign

0.44

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.026

MPC

0.097

ClinPred

0.00082

GERP RS

-4.5

Varity_R

0.056

gMVP

0.21

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