7-100892018-C-T

Variant names:

• chr7-100892018-C-T
• rs2571598
• NM_000665.5:c.1553+316G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000665.5(ACHE):​c.1553+316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,468 control chromosomes in the GnomAD database, including 14,101 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 0.42 (14101 hom., cov: 28)
• Consequence: ACHE NM_000665.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 13 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: Benign. The variant received -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 = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACHE	NM_000665.5	c.1553+316G>A		intron_variant	Intron 3 of 4	ENST00000241069.11	NP_000656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACHE	ENST00000241069.11	c.1553+316G>A		intron_variant	Intron 3 of 4	1	NM_000665.5	ENSP00000241069.5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64148 AN: 151350 Hom.: 14101 Cov.: 28

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64170 AN: 151468 Hom.: 14101 Cov.: 28 AF XY: 0.419 AC XY: 30987 AN XY: 73972

African (AFR) AF: 0.381 AC: 15722 AN: 41280

American (AMR) AF: 0.330 AC: 5025 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3466

East Asian (EAS) AF: 0.152 AC: 779 AN: 5134

South Asian (SAS) AF: 0.396 AC: 1896 AN: 4782

European-Finnish (FIN) AF: 0.483 AC: 5053 AN: 10464

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32871 AN: 67810

Other (OTH) AF: 0.401 AC: 841 AN: 2098

Alfa AF: 0.314 Hom.: 855

Bravo AF: 0.407

Asia WGS AF: 0.279 AC: 975 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	2.5
DANN	Benign	0.78
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2571598; hg19: chr7-100489639;