rs3793798

chr10-49663420-T-Achr10-49663420-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	UniProt
CHAT	NM_020549.5	c.1977+638T>A		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.1977+638T>A		intron_variant		1	NM_020549.5	P2

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

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.361

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

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: rs3793798; hg19: chr10-50871466;