Submissions for variant NM_000497.4(CYP11B1):c.246C>T (p.Asp82=)

gnomAD frequency: 0.33818  dbSNP: rs5283

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385596	SCV000472368	benign	Deficiency of steroid 11-beta-monooxygenase	2018-01-12	criteria provided, single submitter	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.
Illumina Laboratory Services, Illumina	RCV000293653	SCV000472369	benign	Glucocorticoid-remediable aldosteronism	2018-01-12	criteria provided, single submitter	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.
Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	RCV000385596	SCV001424539	benign	Deficiency of steroid 11-beta-monooxygenase	2020-04-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001512040	SCV001719380	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001512040	SCV001830243	benign	not provided	2020-03-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000385596	SCV001876477	benign	Deficiency of steroid 11-beta-monooxygenase	2021-07-30	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001512040	SCV005273578	benign	not provided		criteria provided, single submitter	not provided
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000385596	SCV005400061	benign	Deficiency of steroid 11-beta-monooxygenase	2022-06-24	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (MIM#202010). The mechanism for aldosteronism, glucocorticoid-remediable (MIM#103900) is unclear. (I) 0108 - This gene is associated with both recessive and dominant disease. Recessive disease is caused by biallelic coding variants. Dominant disease is caused by a fusion event between the regulatory region of CYP11B1 and coding region of CYP11B2 (OMIM). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0252 - This variant is homozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (MIM#202010) (gnomAD v2: 64738 heterozygotes, 24408 homozygotes). (SB) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. (SB) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. This variant has been reported multiple times as benign (ClinVar). (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528546	SCV001740435	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528546	SCV001952608	benign	not specified		no assertion criteria provided	clinical testing