10-49614180-T-C

Variant names:

• chr10-49614180-T-C
• rs7923716
• NM_020549.5:c.-10T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020549.5(CHAT):​c.-10T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 20)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHAT NM_020549.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020549.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	NM_020549.5	MANE Select	c.-10T>C		5_prime_UTR	Exon 1 of 15	NP_065574.4	P28329-1
	CHAT	NM_001142933.2		c.-326T>C		5_prime_UTR	Exon 1 of 16	NP_001136405.2	P28329-2
	CHAT	NM_001142929.2		c.-364T>C		5_prime_UTR	Exon 1 of 15	NP_001136401.2	P28329-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAT	ENST00000337653.7	TSL:1 MANE Select	c.-10T>C		5_prime_UTR	Exon 1 of 15	ENSP00000337103.2	P28329-1
	CHAT	ENST00000395562.2	TSL:1	c.-326T>C		5_prime_UTR	Exon 1 of 16	ENSP00000378929.2	P28329-2
	CHAT	ENST00000339797.5	TSL:1	c.-68-2322T>C		intron	N/A	ENSP00000343486.1	P28329-3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000108 AC: 15 AN: 1394354 Hom.: 0 Cov.: 34 AF XY: 0.00000873 AC XY: 6 AN XY: 687672

African (AFR) AF: 0.00 AC: 0 AN: 31498

American (AMR) AF: 0.00 AC: 0 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25146

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4144

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1077858

Other (OTH) AF: 0.00 AC: 0 AN: 57760

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 8265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.64
PhyloP100		-3.1
PromoterAI		0.024	Neutral

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

Other links and lift over

dbSNP: rs7923716; hg19: chr10-50822226;