Variant rs7073028 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020549.5(CHAT):c.1674C>T(p.Ser558=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,614,088 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 111 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 112 hom. )

Consequence

CHAT
NM_020549.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.169

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 10-49655134-C-T is Benign according to our data. Variant chr10-49655134-C-T is described in ClinVar as [Benign]. Clinvar id is 128720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.169 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 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.1674C>T	p.Ser558=	synonymous_variant	12/15	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 linkuse as main transcript	c.1674C>T	p.Ser558=	synonymous_variant	12/15	1	NM_020549.5	ENSP00000337103	P2	P28329-1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3124

AN:

152148

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00541

AC:

1360

AN:

251308

Hom.:

AF XY:

0.00396

AC XY:

538

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0728

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00225

AC:

3285

AN:

1461822

Hom.:

112

Cov.:

AF XY:

0.00196

AC XY:

1423

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000234

Gnomad4 OTH exome

AF:

0.00548

GnomAD4 genome

AF:

0.0205

AC:

3128

AN:

152266

Hom.:

111

Cov.:

AF XY:

0.0198

AC XY:

1474

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0707

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00911

Hom.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

Familial infantile myasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.4

DANN

Benign

0.72

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

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