Variant chr3-165772915-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000055.4(BCHE):c.*467C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 152,134 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0061 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 0 hom. )

Consequence

BCHE
NM_000055.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.152

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
BCHE	NM_000055.4 linkuse as main transcript	c.*467C>G	3_prime_UTR_variant	4/4	ENST00000264381.8
BCHE	NR_137635.2 linkuse as main transcript	n.869C>G	non_coding_transcript_exon_variant	3/3
BCHE	NR_137636.2 linkuse as main transcript	n.2473C>G	non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
BCHE	ENST00000264381.8 linkuse as main transcript	c.*467C>G	3_prime_UTR_variant	4/4	1	NM_000055.4	P1
LINC01322	ENST00000651449.1 linkuse as main transcript	n.1008-72977G>C	intron_variant, non_coding_transcript_variant
BCHE	ENST00000482958.1 linkuse as main transcript	c.*782C>G	3_prime_UTR_variant, NMD_transcript_variant	5/5	3
BCHE	ENST00000497011.5 linkuse as main transcript	c.*666C>G	3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00607

AC:

922

AN:

151810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00322

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00434

GnomAD4 exome

AF:

0.00485

AC:

AN:

206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

128

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00609

AC:

925

AN:

151928

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

384

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00430

Alfa

AF:

0.00583

Hom.:

Bravo

AF:

0.00707

Asia WGS

AF:

0.00116

AC:

AN:

3464

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of butyrylcholinesterase

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.54

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