rs4535

Positions:

Variant summary

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

The NM_000497.4(CYP11B1):c.800-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,610,904 control chromosomes in the GnomAD database, including 1,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 636 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 608 hom. )

Consequence

CYP11B1
NM_000497.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.39

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 (BayesDel_noAF=-0.92).

BP6

Variant 8-142876409-G-A is Benign according to our data. Variant chr8-142876409-G-A is described in ClinVar as [Benign]. Clinvar id is 362160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 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.800-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000292427.10
CYP11B1	NM_001026213.1 linkuse as main transcript	c.800-14C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.800-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000497.4	P1	P15538-1

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7745

AN:

152156

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0139

AC:

3396

AN:

244188

Hom.:

284

AF XY:

0.0103

AC XY:

1363

AN XY:

131910

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000371

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000499

Gnomad OTH exome

AF:

0.00779

GnomAD4 exome

AF:

0.00551

AC:

8041

AN:

1458630

Hom.:

608

Cov.:

AF XY:

0.00482

AC XY:

3497

AN XY:

725280

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000457

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0510

AC:

7773

AN:

152274

Hom.:

636

Cov.:

AF XY:

0.0494

AC XY:

3679

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.00897

Hom.:

Bravo

AF:

0.0592

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 02, 2017	- -

Deficiency of steroid 11-beta-monooxygenase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Glucocorticoid-remediable aldosteronism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.13

DANN

Benign

0.60

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