rs150236872
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_020549.5(CHAT):c.576C>T(p.Asn192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,610,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
CHAT
NM_020549.5 synonymous
NM_020549.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
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 -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 10-49619913-C-T is Benign according to our data. Variant chr10-49619913-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.36 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00156 (237/152034) while in subpopulation AFR AF= 0.00548 (227/41460). AF 95% confidence interval is 0.00489. There are 0 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHAT | NM_020549.5 | c.576C>T | p.Asn192= | synonymous_variant | 3/15 | ENST00000337653.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHAT | ENST00000337653.7 | c.576C>T | p.Asn192= | synonymous_variant | 3/15 | 1 | NM_020549.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00155 AC: 236AN: 151916Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000390 AC: 94AN: 241178Hom.: 0 AF XY: 0.000307 AC XY: 40AN XY: 130328
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GnomAD4 exome AF: 0.000177 AC: 258AN: 1458780Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 119AN XY: 725288
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GnomAD4 genome ? AF: 0.00156 AC: 237AN: 152034Hom.: 0 Cov.: 32 AF XY: 0.00136 AC XY: 101AN XY: 74296
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CHAT-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial infantile myasthenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at