rs114706984

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.635C>T(p.Ala212Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,613,890 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 11 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:7U:2

Conservation

PhyloP100: 1.68

Publications

14 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 3-165830399-G-A is Pathogenic according to our data. Variant chr3-165830399-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 370854.

BP4

Computational evidence support a benign effect (MetaRNN=0.029813468). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 11 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
BCHE	NM_000055.4	MANE Select	c.635C>T	p.Ala212Val	missense	Exon 2 of 4	NP_000046.1
BCHE	NR_137636.2		n.753C>T		non_coding_transcript_exon	Exon 2 of 5
BCHE	NR_137635.2		n.110+6915C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.635C>T	p.Ala212Val	missense	Exon 2 of 4	ENSP00000264381.3
BCHE	ENST00000479451.5	TSL:1	c.107+6915C>T		intron	N/A	ENSP00000418325.1
BCHE	ENST00000482958.1	TSL:3	n.635C>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000419804.1

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

377

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00211

AC:

527

AN:

250210

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00339

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00354

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00391

AC:

5714

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2690

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.000598

AC:

AN:

33470

American (AMR)

AF:

0.00112

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00310

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000267

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.000281

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00482

AC:

5356

AN:

1111900

Other (OTH)

AF:

0.00278

AC:

168

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

377

754

1130

1507

1884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.00247

AC:

376

AN:

152202

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41534

American (AMR)

AF:

0.00131

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00419

AC:

285

AN:

68018

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

102

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:

0.00358

Hom.:

Bravo

AF:

0.00263

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00186

AC:

226

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00362

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of butyrylcholinesterase (5)

not provided (2)

not specified (1)

See cases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.065

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.84

M_CAP

Benign

0.018

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

PhyloP100

1.7

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.36

Sift

Benign

0.31

Sift4G

Benign

0.48

Polyphen

0.35

Vest4

0.22

MVP

0.92

MPC

0.014

ClinPred

0.86

GERP RS

4.8

Varity_R

0.49

gMVP

0.54

Mutation Taster

=88/12

disease causing (ClinVar)

(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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over