NM_000055.4:c.849G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000055.4(BCHE):c.849G>C(p.Glu283Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,926 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.023 ( 78 hom., cov: 32)

Exomes 𝑓: 0.015 ( 252 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.296

Publications

7 publications found

Variant links:

Genes affected

BCHE (HGNC:983): (butyrylcholinesterase) This gene encodes a cholinesterase enzyme and member of the type-B carboxylesterase/lipase family of proteins. The encoded enzyme exhibits broad substrate specificity and is involved in the detoxification of poisons including organophosphate nerve agents and pesticides, and the metabolism of drugs including cocaine, heroin and aspirin. Humans homozygous for certain mutations in this gene exhibit prolonged apnea after administration of the muscle relaxant succinylcholine. [provided by RefSeq, Jul 2016]

BCHE links:

LINC01322 (HGNC:50528): (long intergenic non-protein coding RNA 1322)

LINC01322 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018603504).

BP6

Variant 3-165830185-C-G is Benign according to our data. Variant chr3-165830185-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 254777.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	NM_000055.4	MANE Select	c.849G>C	p.Glu283Asp	missense	Exon 2 of 4	NP_000046.1	P06276
BCHE	NR_137636.2		n.967G>C		non_coding_transcript_exon	Exon 2 of 5
BCHE	NR_137635.2		n.110+7129G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.849G>C	p.Glu283Asp	missense	Exon 2 of 4	ENSP00000264381.3	P06276
BCHE	ENST00000479451.5	TSL:1	c.107+7129G>C		intron	N/A	ENSP00000418325.1	H0Y885
BCHE	ENST00000855337.1		c.849G>C	p.Glu283Asp	missense	Exon 2 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3459

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00951

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.0147

AC:

3685

AN:

250568

AF XY:

0.0147

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.00817

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0146

AC:

21296

AN:

1461684

Hom.:

252

Cov.:

AF XY:

0.0147

AC XY:

10707

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.0632

AC:

2114

AN:

33462

American (AMR)

AF:

0.00864

AC:

386

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

289

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.0266

AC:

2293

AN:

86248

European-Finnish (FIN)

AF:

0.00247

AC:

132

AN:

53416

Middle Eastern (MID)

AF:

0.0435

AC:

251

AN:

5766

European-Non Finnish (NFE)

AF:

0.0133

AC:

14785

AN:

1111888

Other (OTH)

AF:

0.0173

AC:

1043

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1269

2538

3808

5077

6346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0228

AC:

3464

AN:

152242

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1649

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0556

AC:

2311

AN:

41538

American (AMR)

AF:

0.00949

AC:

145

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4828

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

779

AN:

68012

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

167

334

500

667

834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.0255

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.0567

AC:

250

ESP6500EA

AF:

0.0126

AC:

108

ExAC

AF:

0.0157

AC:

1907

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0146

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of butyrylcholinesterase (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.2

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.17

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.30

PrimateAI

Benign

0.26

PROVEAN

Benign

0.61

REVEL

Benign

0.069

Sift

Benign

0.82

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.025

MutPred

0.16

Loss of disorder (P = 0.1294)

MPC

0.014

ClinPred

0.00093

GERP RS

-4.6

Varity_R

0.17

gMVP

0.26

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over