Variant rs1799806 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000302913.8(ACHE):c.1775C>G(p.Pro592Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,454,340 control chromosomes in the GnomAD database, including 138,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10759 hom., cov: 33)

Exomes 𝑓: 0.43 ( 127590 hom. )

Consequence

ACHE
ENST00000302913.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Variant links:

Genes affected

ACHE (HGNC:108): (acetylcholinesterase (Yt blood group)) Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion[provided by RefSeq, Sep 2019]

ACHE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014297366).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACHE	NM_000665.5 linkuse as main transcript	c.1723+132C>G		intron_variant		ENST00000241069.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACHE	ENST00000241069.11 linkuse as main transcript	c.1723+132C>G		intron_variant		1	NM_000665.5	P1	P22303-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54088

AN:

151994

Hom.:

10761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.347

GnomAD3 exomes

AF:

0.361

AC:

30027

AN:

83172

Hom.:

6106

AF XY:

0.365

AC XY:

15683

AN XY:

42948

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

AF:

0.434

AC:

565776

AN:

1302228

Hom.:

127590

Cov.:

AF XY:

0.433

AC XY:

273439

AN XY:

632120

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.380

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.356

AC:

54089

AN:

152112

Hom.:

10759

Cov.:

AF XY:

0.352

AC XY:

26165

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.343

Alfa

AF:

0.415

Hom.:

8653

Bravo

AF:

0.333

TwinsUK

AF:

0.470

AC:

1744

ALSPAC

AF:

0.461

AC:

1776

ESP6500AA

AF:

0.197

AC:

771

ESP6500EA

AF:

0.412

AC:

3296

ExAC

AF:

0.264

AC:

26864

Asia WGS

AF:

0.222

AC:

772

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.36

T;.

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.99

P;P;P;P;P;P

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.50

N;N

REVEL

Benign

0.024

Sift

Benign

0.23

T;T

Sift4G

Benign

0.097

T;T

Polyphen

0.0010

B;B

Vest4

0.091

MPC

1.0

ClinPred

0.0068

GERP RS

1.9

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over