rs3793790

Variant names:

• chr10-49632690-G-A
• rs3793790
• NM_020549.5:c.1111+4905G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-49632690-G-A
• chr10-49632690-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.1111+4905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,972 control chromosomes in the GnomAD database, including 34,454 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 0.67 (34454 hom., cov: 32)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 20 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1111+4905G>A		intron_variant	Intron 7 of 14	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1111+4905G>A		intron_variant	Intron 7 of 14	1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101888 AN: 151854 Hom.: 34438 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.671 AC: 101947 AN: 151972 Hom.: 34454 Cov.: 32 AF XY: 0.672 AC XY: 49948 AN XY: 74278

African (AFR) AF: 0.621 AC: 25709 AN: 41412

American (AMR) AF: 0.749 AC: 11442 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2218 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3988 AN: 5156

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4824

European-Finnish (FIN) AF: 0.730 AC: 7730 AN: 10582

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46034 AN: 67932

Other (OTH) AF: 0.682 AC: 1440 AN: 2110

Alfa AF: 0.653 Hom.: 26026

Bravo AF: 0.675

Asia WGS AF: 0.655 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.46
PhyloP100		-0.82
Mutation Taster		=99/1	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: rs3793790; hg19: chr10-50840736; COSMIC: COSV60321111; COSMIC: COSV60321111;