rs9657021

chr8-142877856-T-Cchr8-142877856-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.13 (3030 hom., cov: 34)
  • Exomes 𝑓: 0.042 (3730 hom.)
• Consequence: CYP11B1 NM_000497.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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]

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]

ACMG classification

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/exons	MANE	UniProt
CYP11B1	NM_000497.4	c.396-634A>G		intron_variant		ENST00000292427.10
CYP11B1	NM_001026213.1	c.396-634A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B1	ENST00000292427.10	c.396-634A>G		intron_variant		1	NM_000497.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19641 AN: 152088 Hom.: 3018 Cov.: 34

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

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.: 31 AF XY: 0.0418 AC XY: 29761 AN XY: 712720

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.: 34 AF XY: 0.127 AC XY: 9477 AN XY: 74430

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

Other links and lift over

dbSNP: rs9657021; hg19: chr8-143959272; COSMIC: COSV52825440; COSMIC: COSV52825440;