rs6537545

Variant names:

• chr10-49651203-A-G
• rs6537545
• NM_020549.5:c.1512-681A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-49651203-A-G
• chr10-49651203-A-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.1512-681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,172 control chromosomes in the GnomAD database, including 11,736 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 0.38 (11736 hom., cov: 29)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5	c.1512-681A>G		intron_variant	Intron 10 of 14	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7	c.1512-681A>G		intron_variant	Intron 10 of 14	1	NM_020549.5	ENSP00000337103.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57455 AN: 151054 Hom.: 11734 Cov.: 29

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.380 AC: 57461 AN: 151172 Hom.: 11736 Cov.: 29 AF XY: 0.373 AC XY: 27536 AN XY: 73784

African (AFR) AF: 0.230 AC: 9496 AN: 41252

American (AMR) AF: 0.388 AC: 5895 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1540 AN: 3464

East Asian (EAS) AF: 0.309 AC: 1574 AN: 5086

South Asian (SAS) AF: 0.479 AC: 2273 AN: 4750

European-Finnish (FIN) AF: 0.310 AC: 3240 AN: 10468

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32106 AN: 67650

Other (OTH) AF: 0.401 AC: 839 AN: 2090

Alfa AF: 0.418 Hom.: 1736

Bravo AF: 0.374

Asia WGS AF: 0.396 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.99
DANN	Benign	0.65
PhyloP100		-0.79
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: rs6537545; hg19: chr10-50859249;