rs10082479

Positions:

• chr10-49621173-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	UniProt
CHAT	NM_020549.5	c.698+560A>T		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.698+560A>T		intron_variant		1	NM_020549.5	P2

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

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.199

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

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: rs10082479; hg19: chr10-50829219;