dbSNP rs9657021: CYP11B1:c.396-634A>G (chr8-142877856-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000497.4(CYP11B1):c.396-634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,583,204 control chromosomes in the GnomAD database, including 6,760 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.13 ( 3030 hom., cov: 34)

Exomes 𝑓: 0.042 ( 3730 hom. )

Consequence

CYP11B1
NM_000497.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.778

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11B1	NM_000497.4 link	c.396-634A>G		intron_variant	Intron 2 of 8	ENST00000292427.10	NP_000488.3	P15538-1Q8TDD0
CYP11B1	NM_001026213.1 link	c.396-634A>G		intron_variant	Intron 2 of 7		NP_001021384.1	P15538-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP11B1	ENST00000292427.10 link	c.396-634A>G		intron_variant	Intron 2 of 8	1	NM_000497.4	ENSP00000292427.5		P15538-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19641

AN:

152088

Hom.:

3018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0625

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.0787

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.0375

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.0663

AC:

14592

AN:

220204

Hom.:

1317

AF XY:

0.0615

AC XY:

7507

AN XY:

122080

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.0506

Gnomad EAS exome

AF:

0.0794

Gnomad SAS exome

AF:

0.0789

Gnomad FIN exome

AF:

0.0407

Gnomad NFE exome

AF:

0.0278

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0416

AC:

59527

AN:

1430998

Hom.:

3730

Cov.:

AF XY:

0.0418

AC XY:

29761

AN XY:

712720

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.0523

Gnomad4 ASJ exome

AF:

0.0519

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.0751

Gnomad4 FIN exome

AF:

0.0386

Gnomad4 NFE exome

AF:

0.0258

Gnomad4 OTH exome

AF:

0.0609

GnomAD4 genome

AF:

0.129

AC:

19694

AN:

152206

Hom.:

3030

Cov.:

AF XY:

0.127

AC XY:

9477

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.369

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.0789

Gnomad4 SAS

AF:

0.0822

Gnomad4 FIN

AF:

0.0375

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.0426

Hom.:

465

Bravo

AF:

0.143

Asia WGS

AF:

0.100

AC:

348

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.1

DANN

Benign

0.74

La Branchor

0.57

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over