NM_000055.4:c.1518-12451T>C

Variant names:

• chr3-165798762-A-G
• rs4680662
• NM_000055.4:c.1518-12451T>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.1518-12451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,932 control chromosomes in the GnomAD database, including 33,946 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 0.64 (33946 hom., cov: 32)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1518-12451T>C		intron_variant	Intron 2 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.111-12451T>C		intron_variant	Intron 1 of 2
BCHE	NR_137636.2	n.1636-12451T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1518-12451T>C		intron_variant	Intron 2 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97812 AN: 151816 Hom.: 33928 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.644 AC: 97848 AN: 151932 Hom.: 33946 Cov.: 32 AF XY: 0.650 AC XY: 48242 AN XY: 74246

African (AFR) AF: 0.360 AC: 14912 AN: 41428

American (AMR) AF: 0.687 AC: 10478 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4018 AN: 5154

South Asian (SAS) AF: 0.755 AC: 3640 AN: 4822

European-Finnish (FIN) AF: 0.833 AC: 8788 AN: 10556

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 51157 AN: 67938

Other (OTH) AF: 0.654 AC: 1382 AN: 2112

Alfa AF: 0.721 Hom.: 51800

Bravo AF: 0.622

Asia WGS AF: 0.715 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.75
PhyloP100		0.71
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: rs4680662; hg19: chr3-165516550;