NM_000055.4(BCHE):c.1584T>A (p.Tyr528Ter) AND Deficiency of butyrylcholinesterase

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Feb 28, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000671148.11

Allele description [Variation Report for NM_000055.4(BCHE):c.1584T>A (p.Tyr528Ter)]

NM_000055.4(BCHE):c.1584T>A (p.Tyr528Ter)

Gene:

BCHE:butyrylcholinesterase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.1

Genomic location:

Preferred name:

NM_000055.4(BCHE):c.1584T>A (p.Tyr528Ter)

HGVS:

NC_000003.12:g.165786245A>T
NG_009031.1:g.56221T>A
NM_000055.4:c.1584T>AMANE SELECT
NP_000046.1:p.Tyr528Ter
NC_000003.11:g.165504033A>T
NM_000055.2:c.1584T>A
NR_137635.2:n.177T>A
NR_137636.2:n.1702T>A

Protein change:

Y528*

Links:

dbSNP: rs760485585

NCBI 1000 Genomes Browser:

rs760485585

Molecular consequence:

NR_137635.2:n.177T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_137636.2:n.1702T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000055.4:c.1584T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Deficiency of butyrylcholinesterase (BCHED)
Synonyms:: Butyrylcholinesterase deficiency; BCHE deficiency; CHE1 deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015270; MedGen: C1283400; OMIM: 617936

Recent activity

Clear Turn Off Turn On

Rattus norvegicus guanine nucleotide binding protein-like 2 (nucleolar), mRNA (c...
Rattus norvegicus guanine nucleotide binding protein-like 2 (nucleolar), mRNA (cDNA clone MGC:116342 IMAGE:7382617), complete cds
gi|68534383|gb|BC099173.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000796098	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Dec 1, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25525159, 8554068, 15781196 Citation Link,
SCV000915034	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002022025	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004813662	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 28, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Help

Summary from all submissions

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

Citations

PubMed

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ.

Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.

PubMed [citation]

PMID:: 25525159
PMCID:: PMC4362528

Four new mutations in the BCHE gene of human butyrylcholinesterase in a Brazilian blood donor sample.

Souza RL, Mikami LR, Maegawa RO, Chautard-Freire-Maia EA.

Mol Genet Metab. 2005 Apr;84(4):349-53. Epub 2005 Jan 24.

PubMed [citation]

PMID:: 15781196

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000796098.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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

From Illumina Laboratory Services, Illumina, SCV000915034.1

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

Description

The BCHE c.1584T>A (p.Tyr528Ter) stop-gained variant, also referred to as BCHE*500STOP, has been reported in a compound heterozygous state with a frameshift variant in one individual who was described as having sensitivity to succinylcholine and showed no BCHE protein activity in a plasma sample (Primo-Parmo et al. 1996). Control data are unavailable for this variant, which is reported at a frequency of 0.00018 in the Latino population of the Exome Aggregation Consortium, but this is based on two alleles so the variant is presumed to be rare. Due to the potential impact of stop-gained variants and the evidence from the literature, the p.Tyr528Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for butyrylcholinesterase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 Revvity Omics, Revvity, SCV002022025.3

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

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004813662.1

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

Description

Variant summary: BCHE c.1584T>A (p.Tyr528X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 6.4e-05 in 250512 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in BCHE causing Deficiency Of Butyrylcholine Esterase (6.4e-05 vs 0.016), allowing no conclusion about variant significance. c.1584T>A has been reported in the literature in an individual affected with Deficiency Of Butyrylcholine Esterase who was compound heterozygous with another pathogenic variant (Primo-Parmo_1996). The following publication has been ascertained in the context of this evaluation (PMID: 8554068). ClinVar contains an entry for this variant (Variation ID: 555346). Based on the evidence outlined above, the variant was 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

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine