Genetic Variant BCHE:p.Ser594Ile (chr3-165773410-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000055.4(BCHE):c.1781G>T(p.Ser594Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,610,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

BCHE
NM_000055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

Publications

0 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18664286).

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.1781G>T	p.Ser594Ile	missense	Exon 4 of 4	NP_000046.1	P06276
BCHE	NR_137635.2		n.374G>T		non_coding_transcript_exon	Exon 3 of 3
BCHE	NR_137636.2		n.1978G>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1781G>T	p.Ser594Ile	missense	Exon 4 of 4	ENSP00000264381.3	P06276
BCHE	ENST00000479451.5	TSL:1	c.371G>T	p.Ser124Ile	missense	Exon 3 of 3	ENSP00000418325.1	H0Y885
BCHE	ENST00000855337.1		c.1844G>T	p.Ser615Ile	missense	Exon 5 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000603

AC:

AN:

248900

AF XY:

0.0000520

show subpopulations

Gnomad AFR exome

AF:

0.000866

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1458586

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725652

show subpopulations

African (AFR)

AF:

0.000629

AC:

AN:

33402

American (AMR)

AF:

0.0000224

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

86066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109640

Other (OTH)

AF:

0.0000498

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000296

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.000990

AC:

AN:

41428

American (AMR)

AF:

0.000197

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

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:

0.000329

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

Eigen

Benign

-0.078

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.5

PhyloP100

3.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.29

Vest4

0.51

MVP

0.86

MPC

0.040

ClinPred

0.15

GERP RS

4.3

Varity_R

0.61

gMVP

0.53

Mutation Taster

=64/36

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over