rs1917813

Positions:

• chr10-49649789-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020549.5(CHAT):​c.1511+153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,402 control chromosomes in the GnomAD database, including 11,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.38 (11868 hom., cov: 31)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-49649789-T-C is Benign according to our data. Variant chr10-49649789-T-C is described in ClinVar as [Benign]. Clinvar id is 678350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.1511+153T>C		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.1511+153T>C		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57755 AN: 151298 Hom.: 11868 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.382 AC: 57760 AN: 151402 Hom.: 11868 Cov.: 31 AF XY: 0.376 AC XY: 27774 AN XY: 73934

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.408

Alfa AF: 0.447 Hom.: 7229

Bravo AF: 0.373

Asia WGS AF: 0.392 AC: 1368 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.7
DANN	Benign	0.53

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: rs1917813; hg19: chr10-50857835;