chr3-165784921-A-T

Variant names:

• chr3-165784921-A-T
• rs2668196
• NM_000055.4:c.1684+1224T>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+1224T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 151,530 control chromosomes in the GnomAD database, including 43,898 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 0.76 (43898 hom., cov: 31)
• Consequence: BCHE NM_000055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 9 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=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1684+1224T>A		intron_variant	Intron 3 of 3	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.277+1224T>A		intron_variant	Intron 2 of 2
BCHE	NR_137636.2	n.1802+1224T>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1684+1224T>A		intron_variant	Intron 3 of 3	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114608 AN: 151412 Hom.: 43869 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.757 AC: 114678 AN: 151530 Hom.: 43898 Cov.: 31 AF XY: 0.760 AC XY: 56309 AN XY: 74076

African (AFR) AF: 0.629 AC: 26015 AN: 41368

American (AMR) AF: 0.755 AC: 11433 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2867 AN: 3464

East Asian (EAS) AF: 0.778 AC: 4010 AN: 5152

South Asian (SAS) AF: 0.788 AC: 3797 AN: 4820

European-Finnish (FIN) AF: 0.888 AC: 9392 AN: 10574

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.805 AC: 54493 AN: 67694

Other (OTH) AF: 0.758 AC: 1594 AN: 2104

Alfa AF: 0.780 Hom.: 5779

Bravo AF: 0.740

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.59
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2668196; hg19: chr3-165502709;