rs3757869

Variant names:

• chr7-100896377-T-C
• rs3757869
• ENST00000445236.3:c.-21+176A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-100896377-T-C
• chr7-100896377-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367918.1(ACHE):​c.178+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: ACHE NM_001367918.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 8 publications found

Genes affected

ACHE (HGNC:108): (acetylcholinesterase (Yt blood group)) Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion[provided by RefSeq, Sep 2019]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367918.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACHE	NM_001367918.1		c.178+176A>G		intron	N/A	NP_001354847.1
	ACHE	NM_001367919.2		c.178+176A>G		intron	N/A	NP_001354848.1
	ACHE	NR_160407.1		n.442+176A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACHE	ENST00000445236.3	TSL:1	c.-21+176A>G		intron	N/A	ENSP00000400933.3
	ACHE	ENST00000894905.1		c.-144A>G		5_prime_UTR	Exon 2 of 6	ENSP00000564964.1
	ACHE	ENST00000894903.1		c.-21+3A>G		splice_region intron	N/A	ENSP00000564962.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.1
DANN	Benign	0.64
PhyloP100		0.83
PromoterAI		0.017	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3757869; hg19: chr7-100493998;