chr3-165775936-C-T

Variant names:

• chr3-165775936-C-T
• rs2668207
• NM_000055.4:c.1685-2430G>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.1685-2430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,642 control chromosomes in the GnomAD database, including 23,648 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 0.52 (23648 hom., cov: 32)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 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.1685-2430G>A		intron	N/A	NP_000046.1
	BCHE	NR_137635.2		n.278-2430G>A		intron	N/A
	BCHE	NR_137636.2		n.1881+1781G>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.1685-2430G>A		intron	N/A	ENSP00000264381.3
	BCHE	ENST00000479451.5	TSL:1	c.275-2430G>A		intron	N/A	ENSP00000418325.1
	BCHE	ENST00000482958.1	TSL:3	n.*191-2430G>A		intron	N/A	ENSP00000419804.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78088 AN: 151522 Hom.: 23630 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.515 AC: 78110 AN: 151642 Hom.: 23648 Cov.: 32 AF XY: 0.525 AC XY: 38886 AN XY: 74100

African (AFR) AF: 0.172 AC: 7129 AN: 41382

American (AMR) AF: 0.601 AC: 9158 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3411 AN: 5166

South Asian (SAS) AF: 0.635 AC: 3055 AN: 4814

European-Finnish (FIN) AF: 0.774 AC: 8175 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 155 AN: 290

European-Non Finnish (NFE) AF: 0.637 AC: 43160 AN: 67716

Other (OTH) AF: 0.528 AC: 1113 AN: 2106

Alfa AF: 0.601 Hom.: 14296

Bravo AF: 0.484

Asia WGS AF: 0.591 AC: 2042 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.69
PhyloP100		-0.39
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: rs2668207; hg19: chr3-165493724;