10-49655101-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020549.5(CHAT):c.1641T>C(p.His547His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,613,882 control chromosomes in the GnomAD database, including 630,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52514 hom., cov: 32)

Exomes 𝑓: 0.89 ( 578400 hom. )

Consequence

CHAT
NM_020549.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.150

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-49655101-T-C is Benign according to our data. Variant chr10-49655101-T-C is described in ClinVar as [Benign]. Clinvar id is 128719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-49655101-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.1641T>C	p.His547His	synonymous_variant	Exon 12 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.1641T>C	p.His547His	synonymous_variant	Exon 12 of 15	1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.825

AC:

125481

AN:

152022

Hom.:

52510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.765

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.862

Gnomad FIN

AF:

0.893

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.907

Gnomad OTH

AF:

0.848

GnomAD3 exomes

AF:

0.844

AC:

212168

AN:

251374

Hom.:

90623

AF XY:

0.854

AC XY:

116123

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.803

Gnomad SAS exome

AF:

0.866

Gnomad FIN exome

AF:

0.890

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.861

GnomAD4 exome

AF:

0.888

AC:

1297416

AN:

1461742

Hom.:

578400

Cov.:

AF XY:

0.888

AC XY:

645965

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.677

Gnomad4 AMR exome

AF:

0.686

Gnomad4 ASJ exome

AF:

0.854

Gnomad4 EAS exome

AF:

0.785

Gnomad4 SAS exome

AF:

0.866

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.909

Gnomad4 OTH exome

AF:

0.874

GnomAD4 genome

AF:

0.825

AC:

125521

AN:

152140

Hom.:

52514

Cov.:

AF XY:

0.824

AC XY:

61278

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.690

Gnomad4 AMR

AF:

0.765

Gnomad4 ASJ

AF:

0.856

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.862

Gnomad4 FIN

AF:

0.893

Gnomad4 NFE

AF:

0.907

Gnomad4 OTH

AF:

0.841

Alfa

AF:

0.887

Hom.:

139236

Bravo

AF:

0.807

Asia WGS

AF:

0.804

AC:

2798

AN:

3478

EpiCase

AF:

0.905

EpiControl

AF:

0.906

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 19, 2016

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial infantile myasthenia

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 11, 2016

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.97

DANN

Benign

0.40

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