NM_000497.4(CYP11B1):c.1151G>A (p.Arg384Gln) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001386864.7

Allele description [Variation Report for NM_000497.4(CYP11B1):c.1151G>A (p.Arg384Gln)]

NM_000497.4(CYP11B1):c.1151G>A (p.Arg384Gln)

Genes:

LOC106799833:CYP11B1 recombination region [Gene]
CYP11B1:cytochrome P450 family 11 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_000497.4(CYP11B1):c.1151G>A (p.Arg384Gln)

HGVS:

NC_000008.11:g.142875283C>T
NG_007954.1:g.9538G>A
NG_046132.1:g.1150C>T
NM_000497.4:c.1151G>AMANE SELECT
NM_001026213.1:c.1151G>A
NP_000488.3:p.Arg384Gln
NP_000488.3:p.Arg384Gln
NP_001021384.1:p.Arg384Gln
NC_000008.10:g.143956699C>T
NM_000497.3:c.1151G>A

Protein change:

R384Q

Links:

dbSNP: rs764598023

NCBI 1000 Genomes Browser:

rs764598023

Molecular consequence:

NM_000497.4:c.1151G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001026213.1:c.1151G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587253	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15751602, 20089618, 26956189, 8506298, 28492532
SCV002759186	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 31, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001587253

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002759186

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 31, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Update on the prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

Motaghedi R, Betensky BP, Slowinska B, Cerame B, Cabrer M, New MI, Wilson RC.

J Pediatr Endocrinol Metab. 2005 Feb;18(2):133-42.

PubMed [citation]

PMID:: 15751602

Functional consequences of seven novel mutations in the CYP11B1 gene: four mutations associated with nonclassic and three mutations causing classic 11{beta}-hydroxylase deficiency.

Parajes S, Loidi L, Reisch N, Dhir V, Rose IT, Hampel R, Quinkler M, Conway GS, Castro-Feijóo L, Araujo-Vilar D, Pombo M, Dominguez F, Williams EL, Cole TR, Kirk JM, Kaminsky E, Rumsby G, Arlt W, Krone N.

J Clin Endocrinol Metab. 2010 Feb;95(2):779-88. doi: 10.1210/jc.2009-0651. Epub 2010 Jan 20.

PubMed [citation]

PMID:: 20089618
PMCID:: PMC2846960

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587253.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 384 of the CYP11B1 protein (p.Arg384Gln). This variant is present in population databases (rs764598023, gnomAD 0.0009%). This missense change has been observed in individuals with 11-beta-hydroxylase deficiency (PMID: 8506298, 15751602, 20089618, 26956189). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 552238). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP11B1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CYP11B1 function (PMID: 8506298). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV002759186.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in an individual with clinical and biochemical features of 11 beta-hydroxylase deficiency in published literature (Curnow et al., 1993); Functional studies demonstrate a damaging effect (impaired function of CYP11B1 resulting in disrupted enzymatic activity) (Curnow et al., 1993); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8506298)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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