dbSNP rs2686409: BCHE:c.1685-4106C>T (chr3-165777612-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000055.4(BCHE):c.1685-4106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 264,364 control chromosomes in the GnomAD database, including 61,970 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 33228 hom., cov: 33)

Exomes 𝑓: 0.71 ( 28742 hom. )

Consequence

BCHE
NM_000055.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.437

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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	Effect	Exon Rank	Protein	UniProt
BCHE	NM_000055.4	MANE Select	c.1685-4106C>T	intron	N/A	NP_000046.1	P06276
BCHE	NR_137635.2		n.278-4106C>T	intron	N/A
BCHE	NR_137636.2		n.1881+105C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1685-4106C>T	intron	N/A	ENSP00000264381.3	P06276
BCHE	ENST00000479451.5	TSL:1	c.275-4106C>T	intron	N/A	ENSP00000418325.1	H0Y885
BCHE	ENST00000855337.1		c.1748-4106C>T	intron	N/A	ENSP00000525396.1

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

97929

AN:

151658

Hom.:

33209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.753

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.655

GnomAD4 exome

AF:

0.709

AC:

79861

AN:

112588

Hom.:

28742

AF XY:

0.711

AC XY:

46665

AN XY:

65632

show subpopulations

African (AFR)

AF:

0.396

AC:

1113

AN:

2810

American (AMR)

AF:

0.786

AC:

6002

AN:

7640

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

1424

AN:

2196

East Asian (EAS)

AF:

0.793

AC:

3847

AN:

4850

South Asian (SAS)

AF:

0.694

AC:

15880

AN:

22886

European-Finnish (FIN)

AF:

0.785

AC:

3894

AN:

4962

Middle Eastern (MID)

AF:

0.640

AC:

1265

AN:

1978

European-Non Finnish (NFE)

AF:

0.714

AC:

42764

AN:

59876

Other (OTH)

AF:

0.681

AC:

3672

AN:

5390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1059

2118

3176

4235

5294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.646

AC:

97985

AN:

151776

Hom.:

33228

Cov.:

AF XY:

0.653

AC XY:

48425

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.412

AC:

17073

AN:

41452

American (AMR)

AF:

0.754

AC:

11494

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.678

AC:

2350

AN:

3468

East Asian (EAS)

AF:

0.800

AC:

4124

AN:

5156

South Asian (SAS)

AF:

0.717

AC:

3452

AN:

4814

European-Finnish (FIN)

AF:

0.809

AC:

8500

AN:

10508

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.719

AC:

48729

AN:

67820

Other (OTH)

AF:

0.660

AC:

1389

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1699

3398

5098

6797

8496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.577

Hom.:

6096

Bravo

AF:

0.628

Asia WGS

AF:

0.753

AC:

2620

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.8

(source)

DANN

Benign

0.72

PhyloP100

0.44

Mutation Taster

=100/0

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