rs1880677

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.580-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,402,166 control chromosomes in the GnomAD database, including 687,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72504 hom., cov: 32)

Exomes 𝑓: 0.99 ( 615220 hom. )

Consequence

CHAT
NM_020549.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0190

Publications

6 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=-0.89).

BP6

Variant 10-49620460-G-A is Benign according to our data. Variant chr10-49620460-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.580-35G>A		intron_variant	Intron 3 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.580-35G>A		intron_variant	Intron 3 of 14	1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.976

AC:

148381

AN:

152096

Hom.:

72445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.969

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.996

Gnomad OTH

AF:

0.976

GnomAD2 exomes

AF:

0.987

AC:

246908

AN:

250088

AF XY:

0.987

show subpopulations

Gnomad AFR exome

AF:

0.927

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.993

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.995

Gnomad OTH exome

AF:

0.986

GnomAD4 exome

AF:

0.992

AC:

1240024

AN:

1249952

Hom.:

615220

Cov.:

AF XY:

0.991

AC XY:

627515

AN XY:

632972

show subpopulations

African (AFR)

AF:

0.926

AC:

27024

AN:

29190

American (AMR)

AF:

0.991

AC:

44045

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.994

AC:

24534

AN:

24694

East Asian (EAS)

AF:

1.00

AC:

38412

AN:

38416

South Asian (SAS)

AF:

0.968

AC:

79381

AN:

81966

European-Finnish (FIN)

AF:

0.999

AC:

50973

AN:

51000

Middle Eastern (MID)

AF:

0.972

AC:

5209

AN:

5358

European-Non Finnish (NFE)

AF:

0.996

AC:

917573

AN:

921444

Other (OTH)

AF:

0.989

AC:

52873

AN:

53452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

502

1004

1507

2009

2511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.976

AC:

148499

AN:

152214

Hom.:

72504

Cov.:

AF XY:

0.976

AC XY:

72605

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.929

AC:

38552

AN:

41518

American (AMR)

AF:

0.986

AC:

15093

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.992

AC:

3443

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5148

AN:

5148

South Asian (SAS)

AF:

0.968

AC:

4670

AN:

4822

European-Finnish (FIN)

AF:

0.999

AC:

10618

AN:

10624

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.996

AC:

67715

AN:

68010

Other (OTH)

AF:

0.976

AC:

2060

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

178

356

533

711

889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.987

Hom.:

19522

Bravo

AF:

0.973

Asia WGS

AF:

0.983

AC:

3420

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial infantile myasthenia

Benign:1

Jul 22, 2021

Genome-Nilou Lab

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

-0.89

CADD

Benign

5.2

(source)

DANN

Benign

0.83

PhyloP100

0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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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rs1880677

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