rs6433

chr8-142912224-C-T

Variant summary

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

The NM_000498.3(CYP11B2):c.1399-131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,486,664 control chromosomes in the GnomAD database, including 280,522 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 0.69 (37415 hom., cov: 30)
  • Exomes 𝑓: 0.60 (243107 hom.)
• Consequence: CYP11B2 NM_000498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

Genes affected

CYP11B2 (HGNC:2592): (cytochrome P450 family 11 subfamily B member 2) 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. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11B2	NM_000498.3	c.1399-131G>A		intron_variant		ENST00000323110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B2	ENST00000323110.2	c.1399-131G>A		intron_variant		1	NM_000498.3	P1
GML	ENST00000522728.5	c.182-1739C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104268 AN: 151666 Hom.: 37358 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.598 AC: 797666 AN: 1334880 Hom.: 243107 AF XY: 0.601 AC XY: 397707 AN XY: 661688

Gnomad4 AFR exome AF: 0.903

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.688 AC: 104386 AN: 151784 Hom.: 37415 Cov.: 30 AF XY: 0.694 AC XY: 51443 AN XY: 74146

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.690

Alfa AF: 0.593 Hom.: 26281

Bravo AF: 0.697

Asia WGS AF: 0.740 AC: 2574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.53
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6433; hg19: chr8-143993640;