3-165788069-T-C

Variant names:

• chr3-165788069-T-C
• rs1355534
• NM_000055.4:c.1518-1758A>G

Variant summary

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

The NM_000055.4(BCHE):​c.1518-1758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,782 control chromosomes in the GnomAD database, including 34,707 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 0.65 (34707 hom., cov: 31)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 9 publications found

Genes affected

BCHE (HGNC:983): (butyrylcholinesterase) This gene encodes a cholinesterase enzyme and member of the type-B carboxylesterase/lipase family of proteins. The encoded enzyme exhibits broad substrate specificity and is involved in the detoxification of poisons including organophosphate nerve agents and pesticides, and the metabolism of drugs including cocaine, heroin and aspirin. Humans homozygous for certain mutations in this gene exhibit prolonged apnea after administration of the muscle relaxant succinylcholine. [provided by RefSeq, Jul 2016]

LINC01322 (HGNC:50528): (long intergenic non-protein coding RNA 1322)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1518-1758A>G		intron_variant	Intron 2 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.111-1758A>G		intron_variant	Intron 1 of 2
BCHE	NR_137636.2	n.1636-1758A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1518-1758A>G		intron_variant	Intron 2 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.653 AC: 98978 AN: 151664 Hom.: 34687 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.652 AC: 99016 AN: 151782 Hom.: 34707 Cov.: 31 AF XY: 0.660 AC XY: 48954 AN XY: 74190

African (AFR) AF: 0.372 AC: 15401 AN: 41400

American (AMR) AF: 0.691 AC: 10515 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2469 AN: 3466

East Asian (EAS) AF: 0.775 AC: 3994 AN: 5152

South Asian (SAS) AF: 0.756 AC: 3645 AN: 4820

European-Finnish (FIN) AF: 0.876 AC: 9266 AN: 10572

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51290 AN: 67836

Other (OTH) AF: 0.665 AC: 1400 AN: 2106

Alfa AF: 0.726 Hom.: 54977

Bravo AF: 0.627

Asia WGS AF: 0.712 AC: 2471 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs1355534; hg19: chr3-165505857;