rs750309713
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000055.4(BCHE):βc.100delβ(p.Ile34LeufsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000033 ( 0 hom., cov: 32)
Exomes π: 0.000050 ( 0 hom. )
Consequence
BCHE
NM_000055.4 frameshift
NM_000055.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.274
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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;
PP5
?
Variant 3-165830933-AT-A is Pathogenic according to our data. Variant chr3-165830933-AT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 594478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCHE | NM_000055.4 | c.100del | p.Ile34LeufsTer11 | frameshift_variant | 2/4 | ENST00000264381.8 | |
BCHE | NR_137636.2 | n.218del | non_coding_transcript_exon_variant | 2/5 | |||
BCHE | NR_137635.2 | n.110+6380del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCHE | ENST00000264381.8 | c.100del | p.Ile34LeufsTer11 | frameshift_variant | 2/4 | 1 | NM_000055.4 | P1 | |
LINC01322 | ENST00000651449.1 | n.1008-14957del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251020Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135646
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GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461638Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38AN XY: 727108
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Deficiency of butyrylcholinesterase Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 04, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 01, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 25, 2017 | - - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at