rs28933390

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP5BP4BS2

The NM_000055.4(BCHE):c.1253G>T(p.Gly418Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,613,898 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G418A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 17 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:7U:1

Conservation

PhyloP100: 1.39

Publications

28 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: Likely_benign. The variant received -4 ACMG points.

PP5

Variant 3-165829781-C-A is Pathogenic according to our data. Variant chr3-165829781-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 13219.

BP4

Computational evidence support a benign effect (MetaRNN=0.01191321). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 17 AR,Unknown gene

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.1253G>T	p.Gly418Val	missense	Exon 2 of 4	NP_000046.1	P06276
BCHE	NR_137636.2		n.1371G>T		non_coding_transcript_exon	Exon 2 of 5
BCHE	NR_137635.2		n.110+7533G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1253G>T	p.Gly418Val	missense	Exon 2 of 4	ENSP00000264381.3	P06276
BCHE	ENST00000479451.5	TSL:1	c.107+7533G>T		intron	N/A	ENSP00000418325.1	H0Y885
BCHE	ENST00000855337.1		c.1253G>T	p.Gly418Val	missense	Exon 2 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00289

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00313

AC:

784

AN:

250680

AF XY:

0.00322

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00520

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00413

AC:

6034

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

2929

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33472

American (AMR)

AF:

0.00251

AC:

112

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.000719

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00189

AC:

101

AN:

53414

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00487

AC:

5414

AN:

1111880

Other (OTH)

AF:

0.00364

AC:

220

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

380

760

1139

1519

1899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.00312

AC:

475

AN:

152208

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000987

AC:

AN:

41528

American (AMR)

AF:

0.00288

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00526

AC:

358

AN:

68010

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00481

Hom.:

Bravo

AF:

0.00332

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00301

AC:

366

EpiCase

AF:

0.00720

EpiControl

AF:

0.00616

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of butyrylcholinesterase (6)

BCHE-related disorder (1)

BCHE, fluoride 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.52

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.23

PhyloP100

1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

REVEL

Benign

0.077

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.088

Vest4

0.27

MVP

0.85

MPC

0.032

ClinPred

0.052

GERP RS

3.1

Varity_R

0.76

gMVP

0.65

Mutation Taster

=90/10

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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