Variant rs11101192 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020549.5(CHAT):c.1281+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,600,960 control chromosomes in the GnomAD database, including 2,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 276 hom., cov: 33)

Exomes 𝑓: 0.016 ( 1913 hom. )

Consequence

CHAT
NM_020549.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-49646721-G-A is Benign according to our data. Variant chr10-49646721-G-A is described in ClinVar as [Benign]. Clinvar id is 261329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5 linkuse as main transcript	c.1281+47G>A		intron_variant		ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 linkuse as main transcript	c.1281+47G>A		intron_variant		1	NM_020549.5	ENSP00000337103	P2	P28329-1

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4357

AN:

152202

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0987

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0550

AC:

12795

AN:

232518

Hom.:

1222

AF XY:

0.0481

AC XY:

6077

AN XY:

126226

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.00710

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.0445

Gnomad FIN exome

AF:

0.00265

Gnomad NFE exome

AF:

0.000824

Gnomad OTH exome

AF:

0.0313

GnomAD4 exome

AF:

0.0162

AC:

23482

AN:

1448642

Hom.:

1913

Cov.:

AF XY:

0.0161

AC XY:

11565

AN XY:

720548

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.00582

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.0410

Gnomad4 FIN exome

AF:

0.00242

Gnomad4 NFE exome

AF:

0.000769

Gnomad4 OTH exome

AF:

0.0231

GnomAD4 genome

AF:

0.0287

AC:

4364

AN:

152318

Hom.:

276

Cov.:

AF XY:

0.0306

AC XY:

2276

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.0988

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.0452

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.0396

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jul 08, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

DANN

Benign

0.46

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