dbSNP rs55849903: BCHE:c.*349G>A (chr3-165773033-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000055.4(BCHE):c.*349G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 181,914 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 77 hom., cov: 32)

Exomes 𝑓: 0.011 ( 3 hom. )

Consequence

BCHE
NM_000055.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0560

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-165773033-C-T is Benign according to our data. Variant chr3-165773033-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 902451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 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.*349G>A	3_prime_UTR	Exon 4 of 4	NP_000046.1	P06276
BCHE	NR_137635.2		n.751G>A	non_coding_transcript_exon	Exon 3 of 3
BCHE	NR_137636.2		n.2355G>A	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCHE	ENST00000264381.8	TSL:1 MANE Select	c.*349G>A	3_prime_UTR	Exon 4 of 4	ENSP00000264381.3	P06276
BCHE	ENST00000855337.1		c.*349G>A	3_prime_UTR	Exon 5 of 5	ENSP00000525396.1
BCHE	ENST00000855336.1		c.*349G>A	3_prime_UTR	Exon 5 of 5	ENSP00000525395.1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3441

AN:

151724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00979

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.00162

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0239

GnomAD4 exome

AF:

0.0105

AC:

316

AN:

30072

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

167

AN XY:

15688

show subpopulations

African (AFR)

AF:

0.0556

AC:

AN:

522

American (AMR)

AF:

0.00818

AC:

AN:

1834

Ashkenazi Jewish (ASJ)

AF:

0.00731

AC:

AN:

684

East Asian (EAS)

AF:

0.000773

AC:

AN:

1294

South Asian (SAS)

AF:

0.0214

AC:

AN:

3224

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

1448

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00916

AC:

176

AN:

19220

Other (OTH)

AF:

0.00973

AC:

AN:

1748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0227

AC:

3445

AN:

151842

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1638

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0553

AC:

2289

AN:

41414

American (AMR)

AF:

0.00978

AC:

149

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.0231

AC:

111

AN:

4814

European-Finnish (FIN)

AF:

0.00162

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

776

AN:

67958

Other (OTH)

AF:

0.0237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

321

481

642

802

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:

0.0167

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0110

AC:

AN:

3460

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of butyrylcholinesterase (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.73

PhyloP100

0.056

Mutation Taster

=100/0

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

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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