3-165784936-C-T

Variant names:

• chr3-165784936-C-T
• rs829508
• NM_000055.4:c.1684+1209G>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.1684+1209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,440 control chromosomes in the GnomAD database, including 34,579 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 0.65 (34579 hom., cov: 31)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	NM_000055.4	MANE Select	c.1684+1209G>A		intron	N/A	NP_000046.1
	BCHE	NR_137635.2		n.277+1209G>A		intron	N/A
	BCHE	NR_137636.2		n.1802+1209G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1684+1209G>A		intron	N/A	ENSP00000264381.3
	BCHE	ENST00000479451.5	TSL:1	c.274+1209G>A		intron	N/A	ENSP00000418325.1
	BCHE	ENST00000488954.1	TSL:3	c.274+1209G>A		intron	N/A	ENSP00000418504.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98609 AN: 151318 Hom.: 34559 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.651 AC: 98648 AN: 151440 Hom.: 34579 Cov.: 31 AF XY: 0.659 AC XY: 48767 AN XY: 74018

African (AFR) AF: 0.368 AC: 15209 AN: 41306

American (AMR) AF: 0.690 AC: 10452 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2469 AN: 3466

East Asian (EAS) AF: 0.777 AC: 4007 AN: 5158

South Asian (SAS) AF: 0.756 AC: 3647 AN: 4822

European-Finnish (FIN) AF: 0.877 AC: 9266 AN: 10564

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51169 AN: 67670

Other (OTH) AF: 0.664 AC: 1393 AN: 2098

Alfa AF: 0.707 Hom.: 99284

Bravo AF: 0.625

Asia WGS AF: 0.713 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.51
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs829508; hg19: chr3-165502724;