10-49644481-G-C

Position:

• chr10-49644481-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020549.5(CHAT):​c.1112-2024G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,126 control chromosomes in the GnomAD database, including 6,491 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 0.26 (6491 hom., cov: 33)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1112-2024G>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.1112-2024G>C		intron_variant		1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39464 AN: 152008 Hom.: 6498 Cov.: 33

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.259 AC: 39468 AN: 152126 Hom.: 6491 Cov.: 33 AF XY: 0.263 AC XY: 19534 AN XY: 74348

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.282

Alfa AF: 0.220 Hom.: 605

Bravo AF: 0.234

Asia WGS AF: 0.128 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.72

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: rs7903612; hg19: chr10-50852527;