rs868750

chr10-49625793-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020549.5(CHAT):c.933+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 874,318 control chromosomes in the GnomAD database, including 11,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1527 hom., cov: 32)
  • Exomes 𝑓: 0.16 (9892 hom.)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.407

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-49625793-G-A is Benign according to our data. Variant chr10-49625793-G-A is described in ClinVar as [Benign]. Clinvar id is 680208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.933+140G>A		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.933+140G>A		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19570 AN: 152080 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.161 AC: 116279 AN: 722120 Hom.: 9892 AF XY: 0.163 AC XY: 61312 AN XY: 376804

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0811

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.128 AC: 19556 AN: 152198 Hom.: 1527 Cov.: 32 AF XY: 0.126 AC XY: 9370 AN XY: 74422

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.139

Alfa AF: 0.174 Hom.: 3191

Bravo AF: 0.120

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.90
Dann	Benign	0.49

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: rs868750; hg19: chr10-50833839;