rs3802230

chr8-142911448-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000498.3(CYP11B2):c.*532G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 169,460 control chromosomes in the GnomAD database, including 33,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30919 hom., cov: 31)
  • Exomes 𝑓: 0.55 (2771 hom.)
• Consequence: CYP11B2 NM_000498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.444

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-142911448-C-A is Benign according to our data. Variant chr8-142911448-C-A is described in ClinVar as [Benign]. Clinvar id is 362184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11B2	NM_000498.3	c.*532G>T		3_prime_UTR_variant	9/9	ENST00000323110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B2	ENST00000323110.2	c.*532G>T		3_prime_UTR_variant	9/9	1	NM_000498.3	P1
GML	ENST00000522728.5	c.182-2515C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94628 AN: 151922 Hom.: 30897 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.626

GnomAD4 exome AF: 0.549 AC: 9556 AN: 17420 Hom.: 2771 Cov.: 0 AF XY: 0.554 AC XY: 4909 AN XY: 8866

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.623 AC: 94690 AN: 152040 Hom.: 30919 Cov.: 31 AF XY: 0.621 AC XY: 46167 AN XY: 74324

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.621

Alfa AF: 0.582 Hom.: 9256

Bravo AF: 0.629

Asia WGS AF: 0.444 AC: 1548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Corticosterone methyloxidase type 2 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Corticosterone 18-monooxygenase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.0
Dann	Benign	0.46

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: rs3802230; hg19: chr8-143992864; COSMIC: COSV59994900;