dbSNP rs7094248: CHAT:c.1281+648C>G (chr10-49647322-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020549.5(CHAT):c.1281+648C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 154,216 control chromosomes in the GnomAD database, including 15,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 15287 hom., cov: 33)

Exomes 𝑓: 0.44 ( 207 hom. )

Consequence

CHAT
NM_020549.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.306

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.1281+648C>G		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+648C>G		intron_variant	Intron 8 of 14	1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66078

AN:

152008

Hom.:

15289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.448

GnomAD4 exome

AF:

0.444

AC:

927

AN:

2090

Hom.:

207

AF XY:

0.431

AC XY:

445

AN XY:

1032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.434

AC:

185

AN:

426

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

South Asian (SAS)

AF:

0.277

AC:

AN:

130

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.473

AC:

677

AN:

1430

Other (OTH)

AF:

0.368

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.434

AC:

66097

AN:

152126

Hom.:

15287

Cov.:

AF XY:

0.437

AC XY:

32523

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.286

AC:

11850

AN:

41492

American (AMR)

AF:

0.433

AC:

6623

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1789

AN:

3466

East Asian (EAS)

AF:

0.305

AC:

1577

AN:

5168

South Asian (SAS)

AF:

0.342

AC:

1651

AN:

4824

European-Finnish (FIN)

AF:

0.594

AC:

6289

AN:

10586

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34779

AN:

67990

Other (OTH)

AF:

0.442

AC:

930

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1884

3768

5653

7537

9421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.481

Hom.:

2199

Bravo

AF:

0.418

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.50

PhyloP100

-0.31

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over