Variant rs1126680 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000479451.5(BCHE):c.84G>A(p.Leu28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,289,372 control chromosomes in the GnomAD database, including 3,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.055 ( 288 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3237 hom. )

Consequence

BCHE
ENST00000479451.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0600

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 3-165837337-C-T is Benign according to our data. Variant chr3-165837337-C-T is described in ClinVar as [Benign]. Clinvar id is 903492.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
BCHE	NM_000055.4 linkuse as main transcript	c.-32G>A	5_prime_UTR_variant	1/4	ENST00000264381.8
BCHE	NR_137635.2 linkuse as main transcript	n.87G>A	non_coding_transcript_exon_variant	1/3
BCHE	NR_137636.2 linkuse as main transcript	n.87G>A	non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCHE	ENST00000264381.8 linkuse as main transcript	c.-32G>A		5_prime_UTR_variant	1/4	1	NM_000055.4	P1
LINC01322	ENST00000651449.1 linkuse as main transcript	n.1008-8555C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8432

AN:

152112

Hom.:

288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0526

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0655

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0555

AC:

7592

AN:

136714

Hom.:

270

AF XY:

0.0575

AC XY:

4269

AN XY:

74234

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.0309

Gnomad ASJ exome

AF:

0.0724

Gnomad EAS exome

AF:

0.0000952

Gnomad SAS exome

AF:

0.0512

Gnomad FIN exome

AF:

0.0728

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0718

AC:

81690

AN:

1137142

Hom.:

3237

Cov.:

AF XY:

0.0713

AC XY:

39753

AN XY:

557882

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.0316

Gnomad4 ASJ exome

AF:

0.0708

Gnomad4 EAS exome

AF:

0.000623

Gnomad4 SAS exome

AF:

0.0506

Gnomad4 FIN exome

AF:

0.0763

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.0654

GnomAD4 genome

AF:

0.0554

AC:

8432

AN:

152230

Hom.:

288

Cov.:

AF XY:

0.0546

AC XY:

4063

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.0525

Gnomad4 ASJ

AF:

0.0694

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.0477

Gnomad4 FIN

AF:

0.0655

Gnomad4 NFE

AF:

0.0787

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.0700

Hom.:

391

Bravo

AF:

0.0526

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of butyrylcholinesterase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.58

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