chr10-49633658-C-T

Position:

• chr10-49633658-C-T

Variant summary

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

The ENST00000337653.7(CHAT):​c.1111+5873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,108 control chromosomes in the GnomAD database, including 56,631 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 0.86 (56631 hom., cov: 31)
• Consequence: CHAT ENST00000337653.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1111+5873C>T		intron_variant		ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1111+5873C>T		intron_variant		1	NM_020549.5	ENSP00000337103	P2

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130435 AN: 151990 Hom.: 56618 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.858 AC: 130489 AN: 152108 Hom.: 56631 Cov.: 31 AF XY: 0.856 AC XY: 63627 AN XY: 74340

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.867

Alfa AF: 0.906 Hom.: 96075

Bravo AF: 0.835

Asia WGS AF: 0.787 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.62

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: rs3793791; hg19: chr10-50841704;