3-165784936-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCHE	NM_000055.4	c.1684+1209G>A		intron_variant		ENST00000264381.8
BCHE	NR_137635.2	n.277+1209G>A		intron_variant, non_coding_transcript_variant
BCHE	NR_137636.2	n.1802+1209G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCHE	ENST00000264381.8	c.1684+1209G>A		intron_variant		1	NM_000055.4	P1
LINC01322	ENST00000651449.1	n.1008-60956C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.664

Alfa AF: 0.724 Hom.: 29559

Bravo AF: 0.625

Asia WGS AF: 0.713 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.0
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs829508; hg19: chr3-165502724;