GeneBe

3-165830006-GT-G

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000055.4(BCHE):​c.1027delA​(p.Thr343ProfsTer16) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCHE
NM_000055.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

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]
LINC01322 (HGNC:50528): (long intergenic non-protein coding RNA 1322)

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BCHE
NM_000055.4
MANE Select
c.1027delAp.Thr343ProfsTer16
frameshift
Exon 2 of 4NP_000046.1P06276
BCHE
NR_137636.2
n.1145delA
non_coding_transcript_exon
Exon 2 of 5
BCHE
NR_137635.2
n.110+7307delA
intron
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BCHE
ENST00000264381.8
TSL:1 MANE Select
c.1027delAp.Thr343ProfsTer16
frameshift
Exon 2 of 4ENSP00000264381.3P06276
BCHE
ENST00000479451.5
TSL:1
c.107+7307delA
intron
N/AENSP00000418325.1H0Y885
BCHE
ENST00000855337.1
c.1027delAp.Thr343ProfsTer16
frameshift
Exon 2 of 5ENSP00000525396.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461516
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727042
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44622
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26116
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39680
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53374
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111868
Other (OTH)
AF:
0.00
AC:
0
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.6

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

Other links and lift over

dbSNP: rs754214624; hg19: chr3-165547794; COSMIC: COSV52258679; API