rs3802230

Variant names:

• chr8-142911448-C-A
• rs3802230
• NM_000498.3:c.*532G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.444
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 362184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	NM_000498.3	MANE Select	c.*532G>T		3_prime_UTR	Exon 9 of 9	NP_000489.3	P19099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	ENST00000323110.2	TSL:1 MANE Select	c.*532G>T		3_prime_UTR	Exon 9 of 9	ENSP00000325822.2	P19099
	CYP11B2	ENST00000945895.1		c.*532G>T		3_prime_UTR	Exon 9 of 9	ENSP00000615954.1
	CYP11B2	ENST00000945896.1		c.*532G>T		3_prime_UTR	Exon 9 of 9	ENSP00000615955.1

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

African (AFR) AF: 0.861 AC: 434 AN: 504

American (AMR) AF: 0.546 AC: 1564 AN: 2866

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 159 AN: 276

East Asian (EAS) AF: 0.354 AC: 404 AN: 1140

South Asian (SAS) AF: 0.609 AC: 997 AN: 1638

European-Finnish (FIN) AF: 0.608 AC: 186 AN: 306

Middle Eastern (MID) AF: 0.591 AC: 26 AN: 44

European-Non Finnish (NFE) AF: 0.542 AC: 5340 AN: 9850

Other (OTH) AF: 0.560 AC: 446 AN: 796

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

African (AFR) AF: 0.828 AC: 34369 AN: 41514

American (AMR) AF: 0.562 AC: 8578 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2133 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1749 AN: 5162

South Asian (SAS) AF: 0.564 AC: 2711 AN: 4806

European-Finnish (FIN) AF: 0.562 AC: 5937 AN: 10556

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37196 AN: 67938

Other (OTH) AF: 0.621 AC: 1312 AN: 2112

Alfa AF: 0.607 Hom.: 27521

Bravo AF: 0.629

Asia WGS AF: 0.444 AC: 1548 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Corticosterone 18-monooxygenase deficiency (1)
-	-	1	Corticosterone methyloxidase type 2 deficiency (1)
-	-	1	Glucocorticoid-remediable aldosteronism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.46
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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