Variant 3-165773193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.339

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]

BCHE links:

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

LINC01322 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	#exon/exons	MANE
BCHE	NM_000055.4 linkuse as main transcript	c.*189G>A	3_prime_UTR_variant	4/4	ENST00000264381.8
BCHE	NR_137635.2 linkuse as main transcript	n.591G>A	non_coding_transcript_exon_variant	3/3
BCHE	NR_137636.2 linkuse as main transcript	n.2195G>A	non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCHE	ENST00000264381.8 linkuse as main transcript	c.*189G>A		3_prime_UTR_variant	4/4	1	NM_000055.4	P1
LINC01322	ENST00000651449.1 linkuse as main transcript	n.1008-72699C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98120

AN:

151792

Hom.:

33324

Cov.:

show subpopulations

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.:

AF XY:

0.718

AC XY:

137961

AN XY:

192140

show subpopulations

Gnomad4 AFR exome

AF:

0.403

Gnomad4 AMR exome

AF:

0.773

Gnomad4 ASJ exome

AF:

0.678

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.801

Gnomad4 NFE exome

AF:

0.718

Gnomad4 OTH exome

AF:

0.696

GnomAD4 genome

AF:

0.646

AC:

98176

AN:

151910

Hom.:

33343

Cov.:

AF XY:

0.654

AC XY:

48523

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.754

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.810

Gnomad4 NFE

AF:

0.719

Gnomad4 OTH

AF:

0.661

Alfa

AF:

0.682

Hom.:

12011

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Deficiency of butyrylcholinesterase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over