rs10082479

Variant names:

• chr10-49621173-A-T
• rs10082479
• NM_020549.5:c.698+560A>T

Variant summary

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

The NM_020549.5(CHAT):​c.698+560A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,190 control chromosomes in the GnomAD database, including 5,215 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 0.23 (5215 hom., cov: 33)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5	c.698+560A>T		intron_variant	Intron 4 of 14	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.698+560A>T		intron_variant	Intron 4 of 14	1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34177 AN: 152072 Hom.: 5173 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.225 AC: 34286 AN: 152190 Hom.: 5215 Cov.: 33 AF XY: 0.227 AC XY: 16885 AN XY: 74400

African (AFR) AF: 0.411 AC: 17045 AN: 41488

American (AMR) AF: 0.324 AC: 4961 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1200 AN: 5160

South Asian (SAS) AF: 0.117 AC: 563 AN: 4828

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10612

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7928 AN: 68004

Other (OTH) AF: 0.199 AC: 421 AN: 2116

Alfa AF: 0.183 Hom.: 440

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.83
PhyloP100		-0.30
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: rs10082479; hg19: chr10-50829219;