ClinVar Miner

Submissions for variant NM_000055.4(BCHE):c.1177G>C (p.Gly393Arg)

gnomAD frequency: 0.00003  dbSNP: rs115129687
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000490265 SCV000678122 pathogenic Deficiency of butyrylcholinesterase 2017-06-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000490265 SCV002511737 pathogenic Deficiency of butyrylcholinesterase 2022-04-24 criteria provided, single submitter clinical testing Variant summary: BCHE c.1177G>C (p.Gly393Arg) results in a non-conservative amino acid change located in the Carboxylesterase, type B domain (IPR002018) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 249686 control chromosomes, predominantly at a frequency of 0.0013 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in BCHE causing Deficiency Of Butyrylcholine Esterase (0.00012 vs 0.016), allowing no conclusion about variant significance. c.1177G>C has been reported in the literature as BCHE*365R (p.Gly365Arg) or silent allele in homozygous and compound heterozygous genotypes among multiple Japanese individuals affected with Deficiency Of Butyrylcholine Esterase (example, Hada_1992, Sakamoto_2001, Maekawa_1997). These data indicate that the variant is very likely to be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function (example, Hada_1992, Sakamoto_2001). The most pronounced variant effect results in absence of normal serum Butyrylcholine Esterase enzyme activity. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic.
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000490265 SCV000267223 uncertain significance Deficiency of butyrylcholinesterase 2016-03-18 flagged submission reference population

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