NM_000055.4(BCHE):c.1072T>A (p.Leu358Ile) AND Deficiency of butyrylcholinesterase

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jan 13, 2023
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:: RCV000665725.12

Allele description [Variation Report for NM_000055.4(BCHE):c.1072T>A (p.Leu358Ile)]

NM_000055.4(BCHE):c.1072T>A (p.Leu358Ile)

Gene:

BCHE:butyrylcholinesterase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.1

Genomic location:

Preferred name:

NM_000055.4(BCHE):c.1072T>A (p.Leu358Ile)

Other names:

L330I

HGVS:

NC_000003.12:g.165829962A>T
NG_009031.1:g.12504T>A
NM_000055.4:c.1072T>AMANE SELECT
NP_000046.1:p.Leu358Ile
NC_000003.11:g.165547750A>T
NM_000055.2:c.1072T>A
NM_000055.3:c.1072T>A
NR_137636.2:n.1190T>A
P06276:p.Leu358Ile

Protein change:

L358I; LEU330ILE

Links:

UniProtKB: P06276#VAR_002362; OMIM: 177400.0012; dbSNP: rs121918557

NCBI 1000 Genomes Browser:

rs121918557

Molecular consequence:

NM_000055.4:c.1072T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_137636.2:n.1190T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Deficiency of butyrylcholinesterase (BCHED)
Synonyms:: Butyrylcholinesterase deficiency; Deficiency of butyrylcholine esterase; BCHE, silent 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015270; MedGen: C1283400; OMIM: 617936

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000789890	Counsyl	no assertion criteria provided	Uncertain significance (Feb 27, 2017)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8680411, 10404729, 9191541, 9388484
SCV000916008	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (May 5, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9191541, 12417112, 10404729, 8680411, 9388484 Citation Link,
SCV002555813	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jun 10, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9191541, 10404729, 8680411, 12417112, 9388484 Citation Link,
SCV005871438	Juno Genomics, Hangzhou Juno Genomics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005917552	Department of Pathology and Laboratory Medicine, Sinai Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 13, 2023)	germline	research	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

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

Citations

PubMed

Genetic mutations of butyrylcholine esterase identified from phenotypic abnormalities in Japan.

Maekawa M, Sudo K, Dey DC, Ishikawa J, Izumi M, Kotani K, Kanno T.

Clin Chem. 1997 Jun;43(6 Pt 1):924-9.

PubMed [citation]

PMID:: 9191541

Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.

Asanuma K, Yagihashi A, Uehara N, Kida T, Watanabe N.

Clin Chim Acta. 1999 May;283(1-2):33-42.

PubMed [citation]

PMID:: 10404729

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000789890.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	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, SCV000916008.1

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

Description

The BCHE c.1072T>A (p.Leu358Ile) missense variant, also known as p.Leu330Ile, has been reported in at least five studies and is found in a total of 15 individuals with butyrylcholinesterase deficiency, including in two in a homozygous state, in two in a compound heterozygous state, and in eleven in a heterozygous state (Iida et al. 1995; Maekawa et al. 1997; Sudo et al. 1997; Asanuma et al. 1999; Liu et al. 2002). Ten of the 11 heterozygous individuals had a moderate reduction of their serum cholinesterase activity, in contrast to the two homozygous and the two compound heterozygous individuals, who all had a severe reduction of their serum cholinesterase activity. Control data are unavailable for this variant, which is reported at a frequency of 0.00106 in the East Asian population of the Genome Aggregation Database. Expression in HEK293 cells revealed that p.Leu358Ile variant had 20% residual serum cholinesterase activity compared to wild type (Liu et al. 2002). Based on the collective evidence, the p.Leu358Ile variant is classified as pathogenic 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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002555813.1

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

Description

Variant summary: BCHE c.1072T>A (p.Leu358Ile) results in a conservative amino acid change located in the Carboxylesterase, type B of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 249532 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BCHE causing Deficiency Of Butyrylcholine Esterase (8.8e-05 vs 0.016), allowing no conclusion about variant significance. c.1072T>A has been reported in the literature in individuals affected with Deficiency Of Butyrylcholine Esterase (e.g. Iida_1995, Sudo_1997, Liu_2002). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity (Sudo_1997, Liu_2002). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely 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 Juno Genomics, Hangzhou Juno Genomics, Inc, SCV005871438.1

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

Description

PM2_Supporting+PM3_Strong+PS3_Moderate+PP4

#	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

From Department of Pathology and Laboratory Medicine, Sinai Health System, SCV005917552.1

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

Last Updated: Jun 29, 2025

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