3-165787389-A-G

Variant names:

• chr3-165787389-A-G
• rs1355538
• NM_000055.4:c.1518-1078T>C

Variant summary

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

The NM_000055.4(BCHE):​c.1518-1078T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,580 control chromosomes in the GnomAD database, including 17,581 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 0.44 (17581 hom., cov: 32)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1518-1078T>C		intron_variant	Intron 2 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.111-1078T>C		intron_variant	Intron 1 of 2
BCHE	NR_137636.2	n.1636-1078T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1518-1078T>C		intron_variant	Intron 2 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66010 AN: 151462 Hom.: 17565 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.436 AC: 66024 AN: 151580 Hom.: 17581 Cov.: 32 AF XY: 0.446 AC XY: 32990 AN XY: 74048

African (AFR) AF: 0.114 AC: 4709 AN: 41488

American (AMR) AF: 0.520 AC: 7898 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1770 AN: 3460

East Asian (EAS) AF: 0.652 AC: 3345 AN: 5134

South Asian (SAS) AF: 0.576 AC: 2773 AN: 4814

European-Finnish (FIN) AF: 0.678 AC: 7126 AN: 10508

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36755 AN: 67672

Other (OTH) AF: 0.441 AC: 929 AN: 2108

Alfa AF: 0.507 Hom.: 30369

Bravo AF: 0.405

Asia WGS AF: 0.554 AC: 1926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.84
PhyloP100		-0.11
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: rs1355538; hg19: chr3-165505177;