3-165804028-G-C

Variant names:

• chr3-165804028-G-C
• rs12487357
• NM_000055.4:c.1518-17717C>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.1518-17717C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 147,636 control chromosomes in the GnomAD database, including 764 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 0.099 (764 hom., cov: 31)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000055.4. 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
	BCHE	NM_000055.4	MANE Select	c.1518-17717C>G		intron	N/A	NP_000046.1	P06276
	BCHE	NR_137635.2		n.111-17717C>G		intron	N/A
	BCHE	NR_137636.2		n.1636-17717C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1518-17717C>G		intron	N/A	ENSP00000264381.3	P06276
	BCHE	ENST00000479451.5	TSL:1	c.108-17717C>G		intron	N/A	ENSP00000418325.1	H0Y885
	BCHE	ENST00000855337.1		c.1518-12158C>G		intron	N/A	ENSP00000525396.1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14549 AN: 147520 Hom.: 760 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0299

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0825

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0986 AC: 14561 AN: 147636 Hom.: 764 Cov.: 31 AF XY: 0.0981 AC XY: 7021 AN XY: 71592

African (AFR) AF: 0.119 AC: 4835 AN: 40766

American (AMR) AF: 0.153 AC: 2193 AN: 14376

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 248 AN: 3438

East Asian (EAS) AF: 0.138 AC: 676 AN: 4894

South Asian (SAS) AF: 0.0878 AC: 397 AN: 4522

European-Finnish (FIN) AF: 0.0404 AC: 383 AN: 9480

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.0826 AC: 5527 AN: 66942

Other (OTH) AF: 0.118 AC: 240 AN: 2026

Alfa AF: 0.0827 Hom.: 66

Bravo AF: 0.106

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.62
PhyloP100		-0.81
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: rs12487357; hg19: chr3-165521816;