GeneBe

rs3729496

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000460699.5(CHAT):​n.38G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CHAT
ENST00000460699.5 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

Publications

12 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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHATNM_020985.4 linkc.-298G>C 5_prime_UTR_variant Exon 1 of 16 NP_066265.4
CHATNM_020986.4 linkc.-126G>C 5_prime_UTR_variant Exon 1 of 15 NP_066266.4
CHATNM_020984.4 linkc.-68-3357G>C intron_variant Intron 1 of 14 NP_066264.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHATENST00000460699.5 linkn.38G>C non_coding_transcript_exon_variant Exon 1 of 7 1
CHATENST00000481336.5 linkn.27G>C non_coding_transcript_exon_variant Exon 1 of 3 1
CHATENST00000339797.5 linkc.-68-3357G>C intron_variant Intron 1 of 14 1 ENSP00000343486.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
88
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66
African (AFR)
AF:
0.00
AC:
0
AN:
2
American (AMR)
AF:
0.00
AC:
0
AN:
2
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.00
AC:
0
AN:
6
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
64
Other (OTH)
AF:
0.00
AC:
0
AN:
8
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
84337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.7
DANN
Benign
0.86
PhyloP100
0.0050
PromoterAI
-0.060
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3729496; hg19: chr10-50821191; API