VCV000225302.3 - ClinVar

NM_000055.4(BCHE):c.884A>G (p.Lys295Arg)

Germline

Classification

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.

(3)

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.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000055.4(BCHE):c.884A>G (p.Lys295Arg)

Variation ID: 225302 Accession: VCV000225302.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q26.1 3: 165830150 (GRCh38) [ NCBI UCSC ] 3: 165547938 (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	May 25, 2017	Sep 17, 2022	Jul 17, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000055.4:c.884A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000046.1:p.Lys295Arg	missense
NR_137636.2:n.1002A>G		non-coding transcript variant
NC_000003.12:g.165830150T>C
NC_000003.11:g.165547938T>C
NG_009031.1:g.12316A>G

... more HGVS ... less HGVS

Protein change

K295R

Other names

Canonical SPDI

NC_000003.12:165830149:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00020 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00011

1000 Genomes Project 30x 0.00016

Exome Aggregation Consortium (ExAC) 0.00017

1000 Genomes Project 0.00020

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA2692410 dbSNP: rs115624085 VarSome

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
Gene	OMIM	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.
BCHE		-	-	GRCh38 GRCh37	-	-

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.
Deficiency of butyrylcholinesterase	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Feb 24, 2017	RCV000490369.3
not specified	Uncertain significance (1)	criteria provided, single submitter	Jul 17, 2022	RCV002282044.1

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.
Likely pathogenic (Mar 18, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: reference population	None Affected status: unknown Allele origin: germline	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center Accession: SCV000267224.1 First in ClinVar: May 25, 2017 Last updated: May 25, 2017	Publications: PubMed (1) PubMed: 9191541 Number of individuals with the variant: 1 Age: 40-69 years Ethnicity/Population group: East Asian Geographic origin: South Korean
Uncertain significance (Feb 24, 2017)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Deficiency of butyrylcholinesterase Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000800500.1 First in ClinVar: May 25, 2017 Last updated: May 25, 2017	Publications: PubMed (1) PubMed: 9191541
Uncertain significance (Jul 17, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002570717.1 First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022	Publications: PubMed (3) PubMed: 25448037‚ 9191541‚ 15781196 Comment: Variant summary: BCHE c.884A>G (p.Lys295Arg) results in a conservative amino acid change located in the Carboxylesterase, type B domain (IPR002018) of the encoded protein sequence. … (more) Variant summary: BCHE c.884A>G (p.Lys295Arg) results in a conservative amino acid change located in the Carboxylesterase, type B domain (IPR002018) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 249806 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BCHE causing Deficiency Of Butyrylcholine Esterase (0.00011 vs 0.016), allowing no conclusion about variant significance. c.884A>G has been reported in the literature as a "silent allele" in individuals affected with Deficiency Of Butyrylcholine Esterase (example, Maekawa_1997 cited in Lockridge_2015, Souza_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Deficiency Of Butyrylcholine Esterase. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)

Comment:

Variant summary: BCHE c.884A>G (p.Lys295Arg) results in a conservative amino acid change located in the Carboxylesterase, type B domain (IPR002018) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 249806 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BCHE causing Deficiency Of Butyrylcholine Esterase (0.00011 vs 0.016), allowing no conclusion about variant significance. c.884A>G has been reported in the literature as a "silent allele" in individuals affected with Deficiency Of Butyrylcholine Esterase (example, Maekawa_1997 cited in Lockridge_2015, Souza_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Deficiency Of Butyrylcholine Esterase. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses.	Lockridge O	Pharmacology & therapeutics	2015	PMID: 25448037
Four new mutations in the BCHE gene of human butyrylcholinesterase in a Brazilian blood donor sample.	Souza RL	Molecular genetics and metabolism	2005	PMID: 15781196
Genetic mutations of butyrylcholine esterase identified from phenotypic abnormalities in Japan.	Maekawa M	Clinical chemistry	1997	PMID: 9191541

Text-mined citations for rs115624085 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 04, 2024

ClinVar Genomic variation as it relates to human health

NM_000055.4(BCHE):c.884A>G (p.Lys295Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs115624085 ...