rs3810948

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_020549.5(CHAT):c.141C>G(p.Asp47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,547,410 control chromosomes in the GnomAD database, including 3,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 505 hom., cov: 33)

Exomes 𝑓: 0.018 ( 2843 hom. )

Consequence

CHAT
NM_020549.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

CHAT (HGNC:1912): (choline O-acetyltransferase) This gene encodes an enzyme which catalyzes the biosynthesis of the neurotransmitter acetylcholine. This gene product is a characteristic feature of cholinergic neurons, and changes in these neurons may explain some of the symptoms of Alzheimer's disease. Polymorphisms in this gene have been associated with Alzheimer's disease and mild cognitive impairment. Mutations in this gene are associated with congenital myasthenic syndrome associated with episodic apnea. Multiple transcript variants encoding different isoforms have been found for this gene, and some of these variants have been shown to encode more than one isoform. [provided by RefSeq, May 2010]

CHAT 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 (MetaRNN=0.0037957132).

BP6

Variant 10-49614330-C-G is Benign according to our data. Variant chr10-49614330-C-G is described in ClinVar as [Benign]. Clinvar id is 128718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 15	ENST00000337653.7	NP_065574.4	P28329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 link	c.141C>G	p.Asp47Glu	missense_variant	Exon 1 of 15	1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4083

AN:

152154

Hom.:

507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0639

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.0547

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0647

AC:

9538

AN:

147316

Hom.:

1235

AF XY:

0.0597

AC XY:

4745

AN XY:

79502

show subpopulations

Gnomad AFR exome

AF:

0.00516

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.00434

Gnomad EAS exome

AF:

0.415

Gnomad SAS exome

AF:

0.0479

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.0352

GnomAD4 exome

AF:

0.0179

AC:

24998

AN:

1395146

Hom.:

2843

Cov.:

AF XY:

0.0183

AC XY:

12613

AN XY:

687900

show subpopulations

Gnomad4 AFR exome

AF:

0.00340

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.00338

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.0473

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.0320

GnomAD4 genome

AF:

0.0268

AC:

4084

AN:

152264

Hom.:

505

Cov.:

AF XY:

0.0311

AC XY:

2315

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00565

Gnomad4 AMR

AF:

0.0639

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.0549

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.0323

ESP6500AA

AF:

0.00210

AC:

ESP6500EA

AF:

0.00162

AC:

ExAC

AF:

0.0242

AC:

1740

Asia WGS

AF:

0.196

AC:

678

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

May 30, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dec 09, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 13, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial infantile myasthenia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.078

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.070

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.12

Vest4

0.036

MutPred

0.14

Gain of methylation at R42 (P = 0.1266);

MPC

0.23

ClinPred

0.042

GERP RS

3.1

Varity_R

0.24

gMVP

0.064

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