dbSNP rs11101192: CHAT:c.1281+47G>A (chr10-49646721-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 6
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.1281+47G>A		intron_variant	Intron 8 of 14	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.1281+47G>A		intron_variant	Intron 8 of 14	1	NM_020549.5	ENSP00000337103.2		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

GnomAD2 exomes

AF:

0.0550

AC:

12795

AN:

232518

AF XY:

0.0481

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 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

African (AFR)

AF:

0.0300

AC:

993

AN:

33128

American (AMR)

AF:

0.179

AC:

7774

AN:

43372

Ashkenazi Jewish (ASJ)

AF:

0.00582

AC:

151

AN:

25930

East Asian (EAS)

AF:

0.222

AC:

8705

AN:

39268

South Asian (SAS)

AF:

0.0410

AC:

3487

AN:

85104

European-Finnish (FIN)

AF:

0.00242

AC:

128

AN:

52808

Middle Eastern (MID)

AF:

0.00305

AC:

AN:

4256

European-Non Finnish (NFE)

AF:

0.000769

AC:

850

AN:

1104980

Other (OTH)

AF:

0.0231

AC:

1381

AN:

59796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1277

2554

3830

5107

6384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.0287

AC:

4364

AN:

152318

Hom.:

276

Cov.:

AF XY:

0.0306

AC XY:

2276

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0299

AC:

1241

AN:

41574

American (AMR)

AF:

0.0988

AC:

1512

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.236

AC:

1215

AN:

5154

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4826

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68038

Other (OTH)

AF:

0.0250

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

201

402

602

803

1004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0111

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

Jul 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.46

PhyloP100

-1.2

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over