10-49654358-T-C

Position:

• chr10-49654358-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.1635-737T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,082 control chromosomes in the GnomAD database, including 14,541 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 0.43 (14541 hom., cov: 34)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1635-737T>C		intron_variant		ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1635-737T>C		intron_variant		1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65824 AN: 151964 Hom.: 14531 Cov.: 34

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.433 AC: 65869 AN: 152082 Hom.: 14541 Cov.: 34 AF XY: 0.430 AC XY: 31992 AN XY: 74346

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.424

Alfa AF: 0.445 Hom.: 14203

Bravo AF: 0.432

Asia WGS AF: 0.603 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.69

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: rs4838547; hg19: chr10-50862404;