rs7094248

Positions:

• chr10-49647322-C-G
• chr10-49647322-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020549.5(CHAT):​c.1281+648C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 154,216 control chromosomes in the GnomAD database, including 15,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15287 hom., cov: 33)
  • Exomes 𝑓: 0.44 (207 hom.)
• Consequence: CHAT NM_020549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHAT	NM_020549.5	c.1281+648C>G		intron_variant		ENST00000337653.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAT	ENST00000337653.7	c.1281+648C>G		intron_variant		1	NM_020549.5	P2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66078 AN: 152008 Hom.: 15289 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.444 AC: 927 AN: 2090 Hom.: 207 AF XY: 0.431 AC XY: 445 AN XY: 1032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.434 AC: 66097 AN: 152126 Hom.: 15287 Cov.: 33 AF XY: 0.437 AC XY: 32523 AN XY: 74392

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.442

Alfa AF: 0.481 Hom.: 2199

Bravo AF: 0.418

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.50

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: rs7094248; hg19: chr10-50855368;