chr3-165777612-G-A

Variant names:

• chr3-165777612-G-A
• rs2686409
• NM_000055.4:c.1685-4106C>T

Variant summary

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

The NM_000055.4(BCHE):​c.1685-4106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 264,364 control chromosomes in the GnomAD database, including 61,970 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 (33228 hom., cov: 33)
  • Exomes 𝑓: 0.71 (28742 hom.)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 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.1685-4106C>T		intron	N/A	NP_000046.1
	BCHE	NR_137635.2		n.278-4106C>T		intron	N/A
	BCHE	NR_137636.2		n.1881+105C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.1685-4106C>T		intron	N/A	ENSP00000264381.3
	BCHE	ENST00000479451.5	TSL:1	c.275-4106C>T		intron	N/A	ENSP00000418325.1
	BCHE	ENST00000482958.1	TSL:3	n.*191-4106C>T		intron	N/A	ENSP00000419804.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 97929 AN: 151658 Hom.: 33209 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.709 AC: 79861 AN: 112588 Hom.: 28742 AF XY: 0.711 AC XY: 46665 AN XY: 65632

African (AFR) AF: 0.396 AC: 1113 AN: 2810

American (AMR) AF: 0.786 AC: 6002 AN: 7640

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 1424 AN: 2196

East Asian (EAS) AF: 0.793 AC: 3847 AN: 4850

South Asian (SAS) AF: 0.694 AC: 15880 AN: 22886

European-Finnish (FIN) AF: 0.785 AC: 3894 AN: 4962

Middle Eastern (MID) AF: 0.640 AC: 1265 AN: 1978

European-Non Finnish (NFE) AF: 0.714 AC: 42764 AN: 59876

Other (OTH) AF: 0.681 AC: 3672 AN: 5390

GnomAD4 genome AF: 0.646 AC: 97985 AN: 151776 Hom.: 33228 Cov.: 33 AF XY: 0.653 AC XY: 48425 AN XY: 74176

African (AFR) AF: 0.412 AC: 17073 AN: 41452

American (AMR) AF: 0.754 AC: 11494 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4124 AN: 5156

South Asian (SAS) AF: 0.717 AC: 3452 AN: 4814

European-Finnish (FIN) AF: 0.809 AC: 8500 AN: 10508

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48729 AN: 67820

Other (OTH) AF: 0.660 AC: 1389 AN: 2106

Alfa AF: 0.577 Hom.: 6096

Bravo AF: 0.628

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		0.44
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: rs2686409; hg19: chr3-165495400;