3-165814620-A-C

Variant names:

• chr3-165814620-A-C
• rs4680663
• NM_000055.4:c.1517+14897T>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.1517+14897T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 151,942 control chromosomes in the GnomAD database, including 59,446 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 0.88 (59446 hom., cov: 30)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1517+14897T>G		intron_variant	Intron 2 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.110+22694T>G		intron_variant	Intron 1 of 2
BCHE	NR_137636.2	n.1635+14897T>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1517+14897T>G		intron_variant	Intron 2 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134074 AN: 151824 Hom.: 59395 Cov.: 30

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.883 AC: 134185 AN: 151942 Hom.: 59446 Cov.: 30 AF XY: 0.885 AC XY: 65703 AN XY: 74256

African (AFR) AF: 0.806 AC: 33367 AN: 41420

American (AMR) AF: 0.911 AC: 13861 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2932 AN: 3468

East Asian (EAS) AF: 0.916 AC: 4711 AN: 5144

South Asian (SAS) AF: 0.886 AC: 4272 AN: 4824

European-Finnish (FIN) AF: 0.932 AC: 9847 AN: 10568

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.915 AC: 62212 AN: 67992

Other (OTH) AF: 0.875 AC: 1844 AN: 2108

Alfa AF: 0.895 Hom.: 24495

Bravo AF: 0.879

Asia WGS AF: 0.909 AC: 3163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.53
PhyloP100		-0.70
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: rs4680663; hg19: chr3-165532408;