rs3793798

Variant names:

• chr10-49663420-T-A
• rs3793798
• NM_020549.5:c.1977+638T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-49663420-T-A
• chr10-49663420-T-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.1977+638T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,032 control chromosomes in the GnomAD database, including 10,151 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 0.35 (10151 hom., cov: 32)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 4 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: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1977+638T>A		intron_variant	Intron 14 of 14	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1977+638T>A		intron_variant	Intron 14 of 14	1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52966 AN: 151914 Hom.: 10149 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.348 AC: 52975 AN: 152032 Hom.: 10151 Cov.: 32 AF XY: 0.344 AC XY: 25554 AN XY: 74312

African (AFR) AF: 0.178 AC: 7374 AN: 41488

American (AMR) AF: 0.358 AC: 5464 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1948 AN: 5142

South Asian (SAS) AF: 0.414 AC: 1994 AN: 4822

European-Finnish (FIN) AF: 0.329 AC: 3474 AN: 10550

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30251 AN: 67976

Other (OTH) AF: 0.361 AC: 760 AN: 2104

Alfa AF: 0.239 Hom.: 590

Bravo AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.73
PhyloP100		-0.046
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: rs3793798; hg19: chr10-50871466;