rs72499120

Variant names:

• chr8-142911443-G-A
• rs72499120
• NM_000498.3:c.*537C>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.*537C>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 0.062 in 170,354 control chromosomes in the GnomAD database, including 1,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (940 hom., cov: 32)
  • Exomes 𝑓: 0.060 (110 hom.)
• Consequence: CYP11B2 NM_000498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.13
• Publications: 3 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=-1.01).
• BP6: Variant 8-142911443-G-A is Benign according to our data. Variant chr8-142911443-G-A is described in ClinVar as Benign. ClinVar VariationId is 362183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 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.*537C>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.*537C>T		3_prime_UTR	Exon 9 of 9	ENSP00000325822.2	P19099
	CYP11B2	ENST00000945895.1		c.*537C>T		3_prime_UTR	Exon 9 of 9	ENSP00000615954.1
	CYP11B2	ENST00000945896.1		c.*537C>T		3_prime_UTR	Exon 9 of 9	ENSP00000615955.1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9411 AN: 152080 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0605 AC: 1098 AN: 18156 Hom.: 110 Cov.: 0 AF XY: 0.0637 AC XY: 585 AN XY: 9180

African (AFR) AF: 0.0298 AC: 18 AN: 604

American (AMR) AF: 0.101 AC: 289 AN: 2868

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 3 AN: 296

East Asian (EAS) AF: 0.400 AC: 382 AN: 956

South Asian (SAS) AF: 0.101 AC: 171 AN: 1692

European-Finnish (FIN) AF: 0.0491 AC: 16 AN: 326

Middle Eastern (MID) AF: 0.0250 AC: 1 AN: 40

European-Non Finnish (NFE) AF: 0.0176 AC: 185 AN: 10488

Other (OTH) AF: 0.0372 AC: 33 AN: 886

GnomAD4 genome AF: 0.0621 AC: 9459 AN: 152198 Hom.: 940 Cov.: 32 AF XY: 0.0695 AC XY: 5171 AN XY: 74408

African (AFR) AF: 0.0535 AC: 2223 AN: 41516

American (AMR) AF: 0.112 AC: 1720 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2587 AN: 5156

South Asian (SAS) AF: 0.159 AC: 767 AN: 4812

European-Finnish (FIN) AF: 0.0498 AC: 528 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1355 AN: 68024

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0332 Hom.: 196

Bravo AF: 0.0654

Asia WGS AF: 0.283 AC: 982 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	-1.0
CADD	Benign	1.6
DANN	Benign	0.35
PhyloP100		-2.1
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: rs72499120; hg19: chr8-143992859;