rs4680663

Positions:

• chr3-165814620-A-C
• chr3-165814620-A-G
• chr3-165814620-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1517+14897T>G		intron_variant		ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.110+22694T>G		intron_variant, non_coding_transcript_variant
BCHE	NR_137636.2	n.1635+14897T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1517+14897T>G		intron_variant		1	NM_000055.4	ENSP00000264381	P1
LINC01322	ENST00000651449.1	n.1008-31272A>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.875

Alfa AF: 0.899 Hom.: 20006

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4680663; hg19: chr3-165532408;