chr10-49641296-T-G

Position:

• chr10-49641296-T-G

Variant summary

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

The NM_020549.5(CHAT):​c.1112-5209T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,160 control chromosomes in the GnomAD database, including 8,142 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 0.31 (8142 hom., cov: 33)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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 (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1112-5209T>G		intron_variant		ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1112-5209T>G		intron_variant		1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47640 AN: 152042 Hom.: 8144 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.313 AC: 47644 AN: 152160 Hom.: 8142 Cov.: 33 AF XY: 0.309 AC XY: 22993 AN XY: 74386

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.345

Alfa AF: 0.257 Hom.: 894

Bravo AF: 0.309

Asia WGS AF: 0.353 AC: 1230 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	5.0
DANN	Benign	0.35

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: rs1917818; hg19: chr10-50849342;