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GeneBe

rs115126024

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020549.5(CHAT):c.1131G>A(p.Ser377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,172 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 94 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 90 hom. )

Consequence

CHAT
NM_020549.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.55
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 10-49646524-G-A is Benign according to our data. Variant chr10-49646524-G-A is described in ClinVar as [Benign]. Clinvar id is 128716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.55 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHATNM_020549.5 linkuse as main transcriptc.1131G>A p.Ser377= synonymous_variant 8/15 ENST00000337653.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHATENST00000337653.7 linkuse as main transcriptc.1131G>A p.Ser377= synonymous_variant 8/151 NM_020549.5 P2P28329-1

Frequencies

GnomAD3 genomes
AF:
0.0189
AC:
2874
AN:
152208
Hom.:
94
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0645
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00955
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0153
GnomAD3 exomes
AF:
0.00519
AC:
1305
AN:
251316
Hom.:
43
AF XY:
0.00380
AC XY:
517
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0669
Gnomad AMR exome
AF:
0.00402
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000334
Gnomad OTH exome
AF:
0.00440
GnomAD4 exome
AF:
0.00213
AC:
3114
AN:
1461848
Hom.:
90
Cov.:
32
AF XY:
0.00186
AC XY:
1351
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0672
Gnomad4 AMR exome
AF:
0.00449
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000278
Gnomad4 OTH exome
AF:
0.00502
GnomAD4 genome
AF:
0.0189
AC:
2878
AN:
152324
Hom.:
94
Cov.:
33
AF XY:
0.0182
AC XY:
1354
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0644
Gnomad4 AMR
AF:
0.00954
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0151
Alfa
AF:
0.00966
Hom.:
17
Bravo
AF:
0.0220
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000356

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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 31, 2016This 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 submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 15, 2013- -
Familial infantile myasthenia Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingAthena Diagnostics IncNov 06, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
0.41
Dann
Benign
0.88

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.

Other links and lift over

dbSNP: rs115126024; hg19: chr10-50854570; API