rs3793792

Variant names:

• chr10-49642117-G-A
• rs3793792
• NM_020549.5:c.1112-4388G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-49642117-G-A
• chr10-49642117-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020549.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	NM_020549.5	MANE Select	c.1112-4388G>A		intron	N/A	NP_065574.4	P28329-1
	CHAT	NM_001142933.2		c.866-4388G>A		intron	N/A	NP_001136405.2	P28329-2
	CHAT	NM_001142929.2		c.758-4388G>A		intron	N/A	NP_001136401.2	P28329-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	ENST00000337653.7	TSL:1 MANE Select	c.1112-4388G>A		intron	N/A	ENSP00000337103.2	P28329-1
	CHAT	ENST00000395562.2	TSL:1	c.866-4388G>A		intron	N/A	ENSP00000378929.2	P28329-2
	CHAT	ENST00000339797.5	TSL:1	c.758-4388G>A		intron	N/A	ENSP00000343486.1	P28329-3

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

African (AFR) AF: 0.184 AC: 7640 AN: 41470

American (AMR) AF: 0.348 AC: 5322 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3464

East Asian (EAS) AF: 0.226 AC: 1165 AN: 5150

South Asian (SAS) AF: 0.447 AC: 2151 AN: 4816

European-Finnish (FIN) AF: 0.240 AC: 2544 AN: 10580

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.386 AC: 26228 AN: 67932

Other (OTH) AF: 0.343 AC: 722 AN: 2108

Alfa AF: 0.363 Hom.: 44516

Bravo AF: 0.308

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3793792; hg19: chr10-50850163;