rs4838537

chr10-49619675-C-T

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.388-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 1,569,936 control chromosomes in the GnomAD database, including 5,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (748 hom., cov: 32)
  • Exomes 𝑓: 0.050 (4935 hom.)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.293

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=-0.81).
• BP6: Variant 10-49619675-C-T is Benign according to our data. Variant chr10-49619675-C-T is described in ClinVar as [Benign]. Clinvar id is 261335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.388-50C>T		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.388-50C>T		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10336 AN: 152102 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0755

GnomAD3 exomes AF: 0.102 AC: 23667 AN: 231130 Hom.: 2909 AF XY: 0.0914 AC XY: 11495 AN XY: 125790

Gnomad AFR exome AF: 0.0652

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.0802

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0303

Gnomad OTH exome AF: 0.0811

GnomAD4 exome AF: 0.0497 AC: 70489 AN: 1417716 Hom.: 4935 Cov.: 28 AF XY: 0.0490 AC XY: 34631 AN XY: 707044

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.0787

Gnomad4 FIN exome AF: 0.0340

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0620

GnomAD4 genome AF: 0.0681 AC: 10373 AN: 152220 Hom.: 748 Cov.: 32 AF XY: 0.0725 AC XY: 5397 AN XY: 74420

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0464 Hom.: 78

Bravo AF: 0.0885

Asia WGS AF: 0.178 AC: 618 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

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.78

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: rs4838537; hg19: chr10-50827721; COSMIC: COSV60323727;