10-49627736-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_020549.5(CHAT):c.1062G>A(p.Thr354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,614,046 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00043 ( 9 hom. )
Consequence
CHAT
NM_020549.5 synonymous
NM_020549.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.622
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.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 10-49627736-G-A is Benign according to our data. Variant chr10-49627736-G-A is described in ClinVar as [Benign]. Clinvar id is 530663.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.622 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00021 (32/152344) while in subpopulation SAS AF= 0.00559 (27/4828). AF 95% confidence interval is 0.00395. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHAT | NM_020549.5 | c.1062G>A | p.Thr354= | synonymous_variant | 7/15 | ENST00000337653.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHAT | ENST00000337653.7 | c.1062G>A | p.Thr354= | synonymous_variant | 7/15 | 1 | NM_020549.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000832 AC: 209AN: 251242Hom.: 3 AF XY: 0.00121 AC XY: 164AN XY: 135794
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GnomAD4 exome AF: 0.000428 AC: 625AN: 1461702Hom.: 9 Cov.: 32 AF XY: 0.000613 AC XY: 446AN XY: 727158
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial infantile myasthenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at