rs3097

Variant names:

• chr8-142911899-C-T
• rs3097
• NM_000498.3:c.*81G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-142911899-C-T
• chr8-142911899-C-A

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.*81G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,599,268 control chromosomes in the GnomAD database, including 59,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3912 hom., cov: 31)
  • Exomes 𝑓: 0.27 (55203 hom.)
• Consequence: CYP11B2 NM_000498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0500
• Publications: 17 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=-0.8).
• BP6: Variant 8-142911899-C-T is Benign according to our data. Variant chr8-142911899-C-T is described in ClinVar as Benign. ClinVar VariationId is 362191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 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.*81G>A		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.*81G>A		3_prime_UTR	Exon 9 of 9	ENSP00000325822.2	P19099
	CYP11B2	ENST00000945895.1		c.*81G>A		3_prime_UTR	Exon 9 of 9	ENSP00000615954.1
	CYP11B2	ENST00000945896.1		c.*81G>A		3_prime_UTR	Exon 9 of 9	ENSP00000615955.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30343 AN: 151388 Hom.: 3917 Cov.: 31

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.269 AC: 389110 AN: 1447764 Hom.: 55203 Cov.: 30 AF XY: 0.267 AC XY: 192425 AN XY: 719620

African (AFR) AF: 0.0457 AC: 1520 AN: 33248

American (AMR) AF: 0.138 AC: 5965 AN: 43098

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6323 AN: 25680

East Asian (EAS) AF: 0.0608 AC: 2395 AN: 39384

South Asian (SAS) AF: 0.189 AC: 16091 AN: 85132

European-Finnish (FIN) AF: 0.262 AC: 13772 AN: 52576

Middle Eastern (MID) AF: 0.201 AC: 1064 AN: 5292

European-Non Finnish (NFE) AF: 0.297 AC: 327219 AN: 1103556

Other (OTH) AF: 0.247 AC: 14761 AN: 59798

GnomAD4 genome AF: 0.200 AC: 30322 AN: 151504 Hom.: 3912 Cov.: 31 AF XY: 0.196 AC XY: 14477 AN XY: 74018

African (AFR) AF: 0.0526 AC: 2172 AN: 41262

American (AMR) AF: 0.182 AC: 2779 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3466

East Asian (EAS) AF: 0.0605 AC: 306 AN: 5062

South Asian (SAS) AF: 0.186 AC: 894 AN: 4798

European-Finnish (FIN) AF: 0.265 AC: 2798 AN: 10562

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.293 AC: 19874 AN: 67798

Other (OTH) AF: 0.193 AC: 405 AN: 2100

Alfa AF: 0.236 Hom.: 572

Bravo AF: 0.188

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3097; hg19: chr8-143993315; COSMIC: COSV59996750;