3-165777612-G-A

Position:

• chr3-165777612-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCHE	NM_000055.4	c.1685-4106C>T		intron_variant		ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.278-4106C>T		intron_variant
BCHE	NR_137636.2	n.1881+105C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.1685-4106C>T		intron_variant		1	NM_000055.4	ENSP00000264381.3

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

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.714

Gnomad4 OTH exome AF: 0.681

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

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.660

Alfa AF: 0.672 Hom.: 4565

Bravo AF: 0.628

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2686409; hg19: chr3-165495400;