Variant rs1880677 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.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

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:

CHAT (HGNC:):

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=-0.89).

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/exons	MANE	Protein	UniProt
CHAT	NM_020549.5 linkuse as main transcript	c.580-35G>A		intron_variant		ENST00000337653.7	NP_065574.4	P28329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 linkuse as main transcript	c.580-35G>A		intron_variant		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

GnomAD3 exomes

AF:

0.987

AC:

246908

AN:

250088

Hom.:

121930

AF XY:

0.987

AC XY:

133512

AN XY:

135270

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 SAS exome

AF:

0.967

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

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.968

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.996

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.976

AC:

148499

AN:

152214

Hom.:

72504

Cov.:

AF XY:

0.976

AC XY:

72605

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.929

Gnomad4 AMR

AF:

0.986

Gnomad4 ASJ

AF:

0.992

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.968

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.996

Gnomad4 OTH

AF:

0.976

Alfa

AF:

0.988

Hom.:

19179

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Familial infantile myasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.2

DANN

Benign

0.83

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

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