rs3793792

chr10-49642117-G-Achr10-49642117-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020549.5(CHAT):c.1112-4388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,990 control chromosomes in the GnomAD database, including 8,090 homozygotes. 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: 𝑓 0.31 (8090 hom., cov: 32)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.1112-4388G>A		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.1112-4388G>A		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47463 AN: 151872 Hom.: 8092 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47466 AN: 151990 Hom.: 8090 Cov.: 32 AF XY: 0.308 AC XY: 22893 AN XY: 74294

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.343

Alfa AF: 0.374 Hom.: 22177

Bravo AF: 0.308

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	16
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs3793792; hg19: chr10-50850163;