3-165773193-C-T

Variant names:

• chr3-165773193-C-T
• rs3495
• NM_000055.4:c.*189G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000055.4(BCHE):​c.*189G>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 0.696 in 516,674 control chromosomes in the GnomAD database, including 128,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33343 hom., cov: 31)
  • Exomes 𝑓: 0.72 (94890 hom.)
• Consequence: BCHE NM_000055.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.339
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-165773193-C-T is Benign according to our data. Variant chr3-165773193-C-T is described in ClinVar as [Benign]. Clinvar id is 344082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.*189G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.591G>A		non_coding_transcript_exon_variant	Exon 3 of 3
BCHE	NR_137636.2	n.2195G>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.*189G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98120 AN: 151792 Hom.: 33324 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.717 AC: 261519 AN: 364764 Hom.: 94890 Cov.: 4 AF XY: 0.718 AC XY: 137961 AN XY: 192140

African (AFR) AF: 0.403 AC: 4141 AN: 10274

American (AMR) AF: 0.773 AC: 9735 AN: 12588

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 7639 AN: 11266

East Asian (EAS) AF: 0.789 AC: 20282 AN: 25692

South Asian (SAS) AF: 0.699 AC: 21736 AN: 31108

European-Finnish (FIN) AF: 0.801 AC: 19466 AN: 24316

Middle Eastern (MID) AF: 0.629 AC: 1011 AN: 1608

European-Non Finnish (NFE) AF: 0.718 AC: 162643 AN: 226552

Other (OTH) AF: 0.696 AC: 14866 AN: 21360

GnomAD4 genome AF: 0.646 AC: 98176 AN: 151910 Hom.: 33343 Cov.: 31 AF XY: 0.654 AC XY: 48523 AN XY: 74244

African (AFR) AF: 0.412 AC: 17058 AN: 41408

American (AMR) AF: 0.754 AC: 11499 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2350 AN: 3462

East Asian (EAS) AF: 0.800 AC: 4129 AN: 5160

South Asian (SAS) AF: 0.718 AC: 3452 AN: 4810

European-Finnish (FIN) AF: 0.810 AC: 8565 AN: 10576

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48857 AN: 67942

Other (OTH) AF: 0.661 AC: 1393 AN: 2108

Alfa AF: 0.688 Hom.: 63094

Bravo AF: 0.628

Asia WGS AF: 0.752 AC: 2604 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Deficiency of butyrylcholinesterase Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs3495; hg19: chr3-165490981;