ClinVar Genomic variation as it relates to human health
NM_000497.4(CYP11B1):c.1066C>T (p.Gln356Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000497.4(CYP11B1):c.1066C>T (p.Gln356Ter)
Variation ID: 56830 Accession: VCV000056830.16
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8q24.3 8: 142875767 (GRCh38) [ NCBI UCSC ] 8: 143957183 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 30, 2013 Jun 17, 2024 Feb 24, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000497.4:c.1066C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000488.3:p.Gln356Ter nonsense NM_001026213.1:c.1066C>T NP_001021384.1:p.Gln356Ter nonsense NC_000008.11:g.142875767G>A NC_000008.10:g.143957183G>A NG_007954.1:g.9054C>T NG_046132.1:g.1634G>A - Protein change
- Q356*
- Other names
- -
- Canonical SPDI
- NC_000008.11:142875766:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00080 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
Trans-Omics for Precision Medicine (TOPMed) 0.00031
The Genome Aggregation Database (gnomAD) 0.00032
1000 Genomes Project 0.00080
1000 Genomes Project 30x 0.00094
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
CYP11B1 | - | - |
GRCh38 GRCh37 |
209 | 898 | |
LOC106799833 | - | - | - | GRCh38 | - | 614 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 24, 2024 | RCV000050222.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 22, 2024 | RCV000711392.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000763178.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 29, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of steroid 11-beta-monooxygenase
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000790567.1
First in ClinVar: Jul 30, 2013 Last updated: Jul 30, 2013 |
|
|
Pathogenic
(Oct 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000841755.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Glucocorticoid-remediable aldosteronism
Deficiency of steroid 11-beta-monooxygenase
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893776.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
Pathogenic
(May 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of steroid 11-beta-monooxygenase
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002521008.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). Stop-gained (nonsense): predicted to result in a … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000056830 / PMID: 8506298). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hyperpigmentation of the skin (present) , Precocious puberty in males (present) , Hypertensive disorder (present) , Adrenocorticotropic hormone excess (present)
|
|
Pathogenic
(Jul 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of steroid 11-beta-monooxygenase
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099220.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
PVS1, PM2, PM3_Strong
|
|
Pathogenic
(Feb 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of steroid 11-beta-monooxygenase
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215326.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Jan 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000957759.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln356*) in the CYP11B1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln356*) in the CYP11B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP11B1 are known to be pathogenic (PMID: 8506298, 26476331). This variant is present in population databases (rs146124466, gnomAD 0.08%). This premature translational stop signal has been observed in individuals with CYP11B1-related conditions (PMID: 8506298, 12966519, 24022297, 27821898). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 56830). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
Deficiency of steroid 11-beta-monooxygenase
Affected status: not provided
Allele origin:
germline
|
Pediatric Endocrinology Laboratory; Christian Albrechts University of Kiel
Accession: SCV000082801.1
First in ClinVar: Jul 30, 2013 Last updated: Jul 30, 2013 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: description of a new mutation, R384X. | Matallana-Rhoades AM | Colombia medica (Cali, Colombia) | 2016 | PMID: 27821898 |
Phenotypic, metabolic, and molecular genetic characterization of six patients with congenital adrenal hyperplasia caused by novel mutations in the CYP11B1 gene. | Nguyen HH | The Journal of steroid biochemistry and molecular biology | 2016 | PMID: 26476331 |
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations. | Menabò S | European journal of human genetics : EJHG | 2014 | PMID: 24022297 |
Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients. | Abbaszadegan MR | Endocrine | 2013 | PMID: 23345044 |
Congenital adrenal hyperplasia in a Nigerian child with a novel compound heterozygote mutation in CYP11B1. | Andrew M | Clinical endocrinology | 2007 | PMID: 17371482 |
Mutations in CYP11B1 gene: phenotype-genotype correlations. | Zhu YS | American journal of medical genetics. Part A | 2003 | PMID: 12966519 |
Novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency. | Merke DP | The Journal of clinical endocrinology and metabolism | 1998 | PMID: 9435454 |
Single strand conformation polymorphism (SSCP) analysis for the detection of mutations in the CYP11B1 gene. | Skinner CA | The Journal of clinical endocrinology and metabolism | 1996 | PMID: 8964882 |
Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. | Curnow KM | Proceedings of the National Academy of Sciences of the United States of America | 1993 | PMID: 8506298 |
Text-mined citations for rs146124466 ...
HelpRecord last updated Jun 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.