8-142910802-A-G

Variant names:

• chr8-142910802-A-G
• rs3802228
• NM_000498.3:c.*1178T>C

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.*1178T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,038 control chromosomes in the GnomAD database, including 31,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (31160 hom., cov: 32)
  • Exomes 𝑓: 0.67 (4 hom.)
• Consequence: CYP11B2 NM_000498.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.78
• Publications: 13 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=-1.0).
• BP6: Variant 8-142910802-A-G is Benign according to our data. Variant chr8-142910802-A-G is described in ClinVar as Benign. ClinVar VariationId is 362173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	NM_000498.3	MANE Select	c.*1178T>C		3_prime_UTR	Exon 9 of 9	NP_000489.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	ENST00000323110.2	TSL:1 MANE Select	c.*1178T>C		3_prime_UTR	Exon 9 of 9	ENSP00000325822.2
	GML	ENST00000522728.5	TSL:3	c.182-3161A>G		intron	N/A	ENSP00000430799.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94909 AN: 151908 Hom.: 31137 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.667 AC: 8 AN: 12 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.600 AC: 6 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.625 AC: 94971 AN: 152026 Hom.: 31160 Cov.: 32 AF XY: 0.623 AC XY: 46287 AN XY: 74322

African (AFR) AF: 0.835 AC: 34616 AN: 41466

American (AMR) AF: 0.562 AC: 8596 AN: 15284

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

East Asian (EAS) AF: 0.339 AC: 1746 AN: 5158

South Asian (SAS) AF: 0.565 AC: 2728 AN: 4826

European-Finnish (FIN) AF: 0.561 AC: 5923 AN: 10558

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37204 AN: 67942

Other (OTH) AF: 0.623 AC: 1318 AN: 2114

Alfa AF: 0.576 Hom.: 71586

Bravo AF: 0.631

Asia WGS AF: 0.445 AC: 1551 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Corticosterone methyloxidase type 2 deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Glucocorticoid-remediable aldosteronism Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-1.8
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: rs3802228; hg19: chr8-143992218;