rs3810948

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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. 15/21 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

Publications

14 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: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
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 (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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020549.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHAT	NM_020549.5	MANE Select	c.141C>G	p.Asp47Glu	missense	Exon 1 of 15	NP_065574.4
CHAT	NM_001142933.2		c.-176C>G		5_prime_UTR	Exon 1 of 16	NP_001136405.2
CHAT	NM_001142929.2		c.-214C>G		5_prime_UTR	Exon 1 of 15	NP_001136401.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHAT	ENST00000337653.7	TSL:1 MANE Select	c.141C>G	p.Asp47Glu	missense	Exon 1 of 15	ENSP00000337103.2
CHAT	ENST00000395562.2	TSL:1	c.-176C>G		5_prime_UTR	Exon 1 of 16	ENSP00000378929.2
CHAT	ENST00000339797.5	TSL:1	c.-68-2172C>G		intron	N/A	ENSP00000343486.1

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

GnomAD2 exomes

AF:

0.0647

AC:

9538

AN:

147316

AF XY:

0.0597

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 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

African (AFR)

AF:

0.00340

AC:

107

AN:

31516

American (AMR)

AF:

0.117

AC:

4189

AN:

35654

Ashkenazi Jewish (ASJ)

AF:

0.00338

AC:

AN:

25140

East Asian (EAS)

AF:

0.348

AC:

12412

AN:

35700

South Asian (SAS)

AF:

0.0473

AC:

3740

AN:

79056

European-Finnish (FIN)

AF:

0.0300

AC:

1443

AN:

48106

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

4092

European-Non Finnish (NFE)

AF:

0.00105

AC:

1134

AN:

1078130

Other (OTH)

AF:

0.0320

AC:

1846

AN:

57752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1239

2478

3717

4956

6195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.0268

AC:

4084

AN:

152264

Hom.:

505

Cov.:

AF XY:

0.0311

AC XY:

2315

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00565

AC:

235

AN:

41558

American (AMR)

AF:

0.0639

AC:

978

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2058

AN:

5154

South Asian (SAS)

AF:

0.0549

AC:

265

AN:

4826

European-Finnish (FIN)

AF:

0.0295

AC:

313

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00238

AC:

162

AN:

68024

Other (OTH)

AF:

0.0275

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

150

301

451

602

752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.00770

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Familial infantile myasthenia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

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

PhyloP100

2.5

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

PromoterAI

-0.057

Neutral

(source)

Varity_R

0.24

gMVP

0.064

Mutation Taster

=296/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over