rs58788269

chr10-49627830-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020549.5(CHAT):c.1111+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00832 in 1,593,994 control chromosomes in the GnomAD database, including 849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (462 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (387 hom.)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 10-49627830-G-A is Benign according to our data. Variant chr10-49627830-G-A is described in ClinVar as [Benign]. Clinvar id is 261326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.1111+45G>A		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.1111+45G>A		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6371 AN: 152094 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0379

GnomAD3 exomes AF: 0.0117 AC: 2609 AN: 223364 Hom.: 166 AF XY: 0.00787 AC XY: 954 AN XY: 121236

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.00803

Gnomad ASJ exome AF: 0.00123

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0000670

Gnomad NFE exome AF: 0.000992

Gnomad OTH exome AF: 0.00844

GnomAD4 exome AF: 0.00477 AC: 6879 AN: 1441782 Hom.: 387 Cov.: 30 AF XY: 0.00406 AC XY: 2911 AN XY: 717088

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.00943

Gnomad4 ASJ exome AF: 0.000963

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000953

Gnomad4 FIN exome AF: 0.0000215

Gnomad4 NFE exome AF: 0.000683

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0419 AC: 6384 AN: 152212 Hom.: 462 Cov.: 33 AF XY: 0.0399 AC XY: 2971 AN XY: 74426

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0375

Alfa AF: 0.0346 Hom.: 61

Bravo AF: 0.0481

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.8
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs58788269; hg19: chr10-50835876;