3-165835799-G-T

Variant names:

• chr3-165835799-G-T
• rs4680607
• NM_000055.4:c.-9+1515C>A

Variant summary

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

The NM_000055.4(BCHE):​c.-9+1515C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 151,730 control chromosomes in the GnomAD database, including 47,635 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 0.79 (47635 hom., cov: 31)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.-9+1515C>A		intron_variant	Intron 1 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.110+1515C>A		intron_variant	Intron 1 of 2
BCHE	NR_137636.2	n.110+1515C>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.-9+1515C>A		intron_variant	Intron 1 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.791 AC: 119865 AN: 151612 Hom.: 47592 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.791 AC: 119966 AN: 151730 Hom.: 47635 Cov.: 31 AF XY: 0.791 AC XY: 58669 AN XY: 74126

African (AFR) AF: 0.723 AC: 29951 AN: 41432

American (AMR) AF: 0.838 AC: 12752 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2650 AN: 3466

East Asian (EAS) AF: 0.805 AC: 4159 AN: 5166

South Asian (SAS) AF: 0.794 AC: 3822 AN: 4816

European-Finnish (FIN) AF: 0.830 AC: 8763 AN: 10554

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55289 AN: 67760

Other (OTH) AF: 0.775 AC: 1636 AN: 2110

Alfa AF: 0.769 Hom.: 2942

Bravo AF: 0.786

Asia WGS AF: 0.810 AC: 2816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.33
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: rs4680607; hg19: chr3-165553587;