rs1880676

Positions:

chr10-49616071-G-A

Variant summary

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

The NM_001142933.2(CHAT):c.19G>A(p.Asp7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,640 control chromosomes in the GnomAD database, including 47,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3033 hom., cov: 34)

Exomes 𝑓: 0.24 ( 44787 hom. )

Consequence

CHAT
NM_001142933.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.43

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=0.0045491755).

BP6

Variant 10-49616071-G-A is Benign according to our data. Variant chr10-49616071-G-A is described in ClinVar as [Benign]. Clinvar id is 402536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.287-431G>A		intron_variant		ENST00000337653.7	NP_065574.4	P28329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 link	c.287-431G>A		intron_variant		1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27293

AN:

152130

Hom.:

3036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.210

AC:

52261

AN:

248860

Hom.:

6115

AF XY:

0.220

AC XY:

29810

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0416

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.243

AC:

354404

AN:

1460392

Hom.:

44787

Cov.:

AF XY:

0.245

AC XY:

177869

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.0393

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.179

AC:

27284

AN:

152248

Hom.:

3033

Cov.:

AF XY:

0.179

AC XY:

13325

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.237

Hom.:

8758

Bravo

AF:

0.170

TwinsUK

AF:

0.257

AC:

953

ALSPAC

AF:

0.272

AC:

1049

ESP6500AA

AF:

0.0501

AC:

157

ESP6500EA

AF:

0.248

AC:

1775

ExAC

AF:

0.211

AC:

25417

Asia WGS

AF:

0.191

AC:

663

AN:

3478

EpiCase

AF:

0.261

EpiControl

AF:

0.259

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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: MAF -

Familial infantile myasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.6

DANN

Uncertain

0.99

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.13

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Benign

0.81

Vest4

0.051

ClinPred

0.029

GERP RS

3.2

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