3-165773033-C-T

Variant names:

• chr3-165773033-C-T
• rs55849903
• NM_000055.4:c.*349G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (77 hom., cov: 32)
  • Exomes 𝑓: 0.011 (3 hom.)
• Consequence: BCHE NM_000055.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0560
• Publications: 3 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.*349G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.751G>A		non_coding_transcript_exon_variant	Exon 3 of 3
BCHE	NR_137636.2	n.2355G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.*349G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3441 AN: 151724 Hom.: 77 Cov.: 32

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.: 3 Cov.: 0 AF XY: 0.0106 AC XY: 167 AN XY: 15688

African (AFR) AF: 0.0556 AC: 29 AN: 522

American (AMR) AF: 0.00818 AC: 15 AN: 1834

Ashkenazi Jewish (ASJ) AF: 0.00731 AC: 5 AN: 684

East Asian (EAS) AF: 0.000773 AC: 1 AN: 1294

South Asian (SAS) AF: 0.0214 AC: 69 AN: 3224

European-Finnish (FIN) AF: 0.00207 AC: 3 AN: 1448

Middle Eastern (MID) AF: 0.0102 AC: 1 AN: 98

European-Non Finnish (NFE) AF: 0.00916 AC: 176 AN: 19220

Other (OTH) AF: 0.00973 AC: 17 AN: 1748

GnomAD4 genome AF: 0.0227 AC: 3445 AN: 151842 Hom.: 77 Cov.: 32 AF XY: 0.0221 AC XY: 1638 AN XY: 74170

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: 46 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0231 AC: 111 AN: 4814

European-Finnish (FIN) AF: 0.00162 AC: 17 AN: 10476

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 67958

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.0167 Hom.: 11

Bravo AF: 0.0255

Asia WGS AF: 0.0110 AC: 38 AN: 3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Deficiency of butyrylcholinesterase Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55849903; hg19: chr3-165490821;