rs1917810

Variant names:

• chr10-49662025-A-G
• rs1917810
• NM_020549.5:c.1840-620A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020549.5(CHAT):​c.1840-620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,160 control chromosomes in the GnomAD database, including 12,965 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 0.40 (12965 hom., cov: 33)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 11 publications found

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]

CHAT Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 6

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1840-620A>G		intron_variant	Intron 13 of 14	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1840-620A>G		intron_variant	Intron 13 of 14	1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61385 AN: 152042 Hom.: 12956 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.404 AC: 61425 AN: 152160 Hom.: 12965 Cov.: 33 AF XY: 0.402 AC XY: 29883 AN XY: 74386

African (AFR) AF: 0.303 AC: 12597 AN: 41512

American (AMR) AF: 0.380 AC: 5809 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3569 AN: 5170

South Asian (SAS) AF: 0.552 AC: 2657 AN: 4812

European-Finnish (FIN) AF: 0.343 AC: 3635 AN: 10588

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30471 AN: 67992

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.429 Hom.: 8006

Bravo AF: 0.398

Asia WGS AF: 0.601 AC: 2093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.44
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1917810; hg19: chr10-50870071;