rs1126680

Variant names:

• chr3-165837337-C-T
• rs1126680
• ENST00000479451.5:c.84G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000479451.5(BCHE):​c.84G>A​(p.Leu28Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,289,372 control chromosomes in the GnomAD database, including 3,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (288 hom., cov: 32)
  • Exomes 𝑓: 0.072 (3237 hom.)
• Consequence: BCHE ENST00000479451.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0600
• Publications: 28 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 3-165837337-C-T is Benign according to our data. Variant chr3-165837337-C-T is described in ClinVar as Benign. ClinVar VariationId is 903492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479451.5. 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.-32G>A		5_prime_UTR	Exon 1 of 4	NP_000046.1
	BCHE	NR_137635.2		n.87G>A		non_coding_transcript_exon	Exon 1 of 3
	BCHE	NR_137636.2		n.87G>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000479451.5	TSL:1	c.84G>A	p.Leu28Leu	synonymous	Exon 1 of 3	ENSP00000418325.1
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.-32G>A		5_prime_UTR	Exon 1 of 4	ENSP00000264381.3
	BCHE	ENST00000488954.1	TSL:3	c.84G>A	p.Leu28Leu	synonymous	Exon 1 of 3	ENSP00000418504.1

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8432 AN: 152112 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0555 AC: 7592 AN: 136714 AF XY: 0.0575

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.0309

Gnomad ASJ exome AF: 0.0724

Gnomad EAS exome AF: 0.0000952

Gnomad FIN exome AF: 0.0728

Gnomad NFE exome AF: 0.0782

Gnomad OTH exome AF: 0.0588

GnomAD4 exome AF: 0.0718 AC: 81690 AN: 1137142 Hom.: 3237 Cov.: 30 AF XY: 0.0713 AC XY: 39753 AN XY: 557882

African (AFR) AF: 0.0182 AC: 444 AN: 24404

American (AMR) AF: 0.0316 AC: 894 AN: 28262

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 1128 AN: 15940

East Asian (EAS) AF: 0.000623 AC: 8 AN: 12838

South Asian (SAS) AF: 0.0506 AC: 3855 AN: 76194

European-Finnish (FIN) AF: 0.0763 AC: 997 AN: 13060

Middle Eastern (MID) AF: 0.0686 AC: 302 AN: 4400

European-Non Finnish (NFE) AF: 0.0775 AC: 71345 AN: 920524

Other (OTH) AF: 0.0654 AC: 2717 AN: 41520

GnomAD4 genome AF: 0.0554 AC: 8432 AN: 152230 Hom.: 288 Cov.: 32 AF XY: 0.0546 AC XY: 4063 AN XY: 74414

African (AFR) AF: 0.0229 AC: 953 AN: 41558

American (AMR) AF: 0.0525 AC: 803 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5172

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4826

European-Finnish (FIN) AF: 0.0655 AC: 694 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0787 AC: 5352 AN: 68002

Other (OTH) AF: 0.0516 AC: 109 AN: 2112

Alfa AF: 0.0642 Hom.: 528

Bravo AF: 0.0526

Asia WGS AF: 0.0230 AC: 84 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of butyrylcholinesterase (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		-0.060
PromoterAI		-0.059	Neutral
Mutation Taster		=300/0	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: rs1126680; hg19: chr3-165555125;