rs28491316

Variant names:

• chr8-142911245-C-T
• rs28491316
• NM_000498.3:c.*735G>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.*735G>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 0.353 in 152,058 control chromosomes in the GnomAD database, including 11,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (11370 hom., cov: 31)
  • Exomes 𝑓: 0.39 (8 hom.)
• Consequence: CYP11B2 NM_000498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.787
• Publications: 8 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=-0.92).
• BP6: Variant 8-142911245-C-T is Benign according to our data. Variant chr8-142911245-C-T is described in ClinVar as Benign. ClinVar VariationId is 362180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 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.*735G>A		3_prime_UTR	Exon 9 of 9	NP_000489.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	ENST00000323110.2	TSL:1 MANE Select	c.*735G>A		3_prime_UTR	Exon 9 of 9	ENSP00000325822.2
	CYP11B2	ENST00000945895.1		c.*735G>A		3_prime_UTR	Exon 9 of 9	ENSP00000615954.1
	CYP11B2	ENST00000945896.1		c.*735G>A		3_prime_UTR	Exon 9 of 9	ENSP00000615955.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53631 AN: 151844 Hom.: 11374 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.385 AC: 37 AN: 96 Hom.: 8 Cov.: 0 AF XY: 0.393 AC XY: 22 AN XY: 56

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.389 AC: 28 AN: 72

Other (OTH) AF: 0.417 AC: 5 AN: 12

GnomAD4 genome AF: 0.353 AC: 53620 AN: 151962 Hom.: 11370 Cov.: 31 AF XY: 0.358 AC XY: 26599 AN XY: 74258

African (AFR) AF: 0.113 AC: 4690 AN: 41508

American (AMR) AF: 0.416 AC: 6354 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1875 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1615 AN: 5142

South Asian (SAS) AF: 0.403 AC: 1929 AN: 4788

European-Finnish (FIN) AF: 0.483 AC: 5089 AN: 10542

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30665 AN: 67938

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.419 Hom.: 35333

Bravo AF: 0.337

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28491316; hg19: chr8-143992661;