Variant 10-49614146-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020549.5(CHAT):c.-44G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,545,460 control chromosomes in the GnomAD database, including 414,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 28226 hom., cov: 25)

Exomes 𝑓: 0.73 ( 386585 hom. )

Consequence

CHAT
NM_020549.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.494

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-49614146-G-C is Benign according to our data. Variant chr10-49614146-G-C is described in ClinVar as [Benign]. Clinvar id is 261325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAT	NM_020549.5 link	c.-44G>C		5_prime_UTR_variant	Exon 1 of 15	ENST00000337653.7	NP_065574.4	P28329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653 link	c.-44G>C		5_prime_UTR_variant	Exon 1 of 15	1	NM_020549.5	ENSP00000337103.2		P28329-1

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

83524

AN:

150778

Hom.:

28240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.686

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.596

GnomAD3 exomes

AF:

0.630

AC:

89439

AN:

142068

Hom.:

31117

AF XY:

0.656

AC XY:

50419

AN XY:

76844

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.665

Gnomad NFE exome

AF:

0.771

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.733

AC:

1022741

AN:

1394564

Hom.:

386585

Cov.:

AF XY:

0.738

AC XY:

507830

AN XY:

687670

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.372

Gnomad4 SAS exome

AF:

0.787

Gnomad4 FIN exome

AF:

0.666

Gnomad4 NFE exome

AF:

0.775

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.553

AC:

83496

AN:

150896

Hom.:

28226

Cov.:

AF XY:

0.551

AC XY:

40565

AN XY:

73628

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.783

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.768

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.619

Hom.:

4227

Bravo

AF:

0.514

Asia WGS

AF:

0.503

AC:

1753

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Familial infantile myasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over