rs1917813

Variant names:

• chr10-49649789-T-C
• rs1917813
• NM_020549.5:c.1511+153T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020549.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	NM_020549.5	MANE Select	c.1511+153T>C		intron	N/A	NP_065574.4	P28329-1
	CHAT	NM_001142933.2		c.1265+153T>C		intron	N/A	NP_001136405.2	P28329-2
	CHAT	NM_001142929.2		c.1157+153T>C		intron	N/A	NP_001136401.2	P28329-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	ENST00000337653.7	TSL:1 MANE Select	c.1511+153T>C		intron	N/A	ENSP00000337103.2	P28329-1
	CHAT	ENST00000395562.2	TSL:1	c.1265+153T>C		intron	N/A	ENSP00000378929.2	P28329-2
	CHAT	ENST00000339797.5	TSL:1	c.1157+153T>C		intron	N/A	ENSP00000343486.1	P28329-3

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

African (AFR) AF: 0.231 AC: 9506 AN: 41196

American (AMR) AF: 0.391 AC: 5960 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1703 AN: 5092

South Asian (SAS) AF: 0.465 AC: 2231 AN: 4802

European-Finnish (FIN) AF: 0.317 AC: 3290 AN: 10378

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32203 AN: 67936

Other (OTH) AF: 0.408 AC: 857 AN: 2100

Alfa AF: 0.446 Hom.: 8088

Bravo AF: 0.373

Asia WGS AF: 0.392 AC: 1368 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.7
DANN	Benign	0.53
PhyloP100		-1.2
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: rs1917813; hg19: chr10-50857835;