rs1799806

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/19 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

Publications

37 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000302913.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACHE	NM_000665.5	MANE Select	c.1723+132C>G		intron	N/A	NP_000656.1
ACHE	NM_001302621.3		c.1775C>G	p.Pro592Arg	missense	Exon 5 of 5	NP_001289550.1
ACHE	NM_001367918.1		c.1924+132C>G		intron	N/A	NP_001354847.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACHE	ENST00000302913.8	TSL:1	c.1775C>G	p.Pro592Arg	missense	Exon 5 of 5	ENSP00000303211.4
ACHE	ENST00000411582.4	TSL:1	c.1775C>G	p.Pro592Arg	missense	Exon 5 of 5	ENSP00000404865.1
ACHE	ENST00000241069.11	TSL:1 MANE Select	c.1723+132C>G		intron	N/A	ENSP00000241069.5

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

GnomAD2 exomes

AF:

0.361

AC:

30027

AN:

83172

AF XY:

0.365

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 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

African (AFR)

AF:

0.191

AC:

5423

AN:

28454

American (AMR)

AF:

0.254

AC:

5329

AN:

20950

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

7307

AN:

19244

East Asian (EAS)

AF:

0.116

AC:

3922

AN:

33870

South Asian (SAS)

AF:

0.335

AC:

21973

AN:

65576

European-Finnish (FIN)

AF:

0.461

AC:

20805

AN:

45164

Middle Eastern (MID)

AF:

0.381

AC:

1421

AN:

3732

European-Non Finnish (NFE)

AF:

0.463

AC:

477565

AN:

1031628

Other (OTH)

AF:

0.411

AC:

22031

AN:

53610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

18678

37356

56033

74711

93389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14772

29544

44316

59088

73860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.356

AC:

54089

AN:

152112

Hom.:

10759

Cov.:

AF XY:

0.352

AC XY:

26165

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.206

AC:

8550

AN:

41520

American (AMR)

AF:

0.294

AC:

4499

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1325

AN:

3472

East Asian (EAS)

AF:

0.136

AC:

704

AN:

5170

South Asian (SAS)

AF:

0.338

AC:

1629

AN:

4818

European-Finnish (FIN)

AF:

0.457

AC:

4835

AN:

10584

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.461

AC:

31340

AN:

67938

Other (OTH)

AF:

0.343

AC:

726

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1761

3522

5283

7044

8805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.94

PhyloP100

0.19

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.50

REVEL

Benign

0.024

Sift

Benign

0.23

Sift4G

Benign

0.097

Polyphen

0.0010

Vest4

0.091

MPC

1.0

ClinPred

0.0068

GERP RS

1.9

gMVP

0.55

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over