rs139885577

Variant names:

• chr3-165773202-C-T
• rs139885577
• NM_000055.4:c.*180G>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.*180G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 554,916 control chromosomes in the GnomAD database, including 106 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 0.018 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (26 hom.)
• Consequence: BCHE NM_000055.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.421
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCHE	NM_000055.4	c.*180G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000264381.8	NP_000046.1
BCHE	NR_137635.2	n.582G>A		non_coding_transcript_exon_variant	Exon 3 of 3
BCHE	NR_137636.2	n.2186G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCHE	ENST00000264381.8	c.*180G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000055.4	ENSP00000264381.3

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2710 AN: 152010 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00604

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00213 AC: 859 AN: 402790 Hom.: 26 Cov.: 5 AF XY: 0.00159 AC XY: 338 AN XY: 212550

African (AFR) AF: 0.0589 AC: 654 AN: 11110

American (AMR) AF: 0.00298 AC: 42 AN: 14100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12136

East Asian (EAS) AF: 0.00 AC: 0 AN: 27632

South Asian (SAS) AF: 0.000142 AC: 5 AN: 35240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27082

Middle Eastern (MID) AF: 0.00171 AC: 3 AN: 1758

European-Non Finnish (NFE) AF: 0.000112 AC: 28 AN: 250524

Other (OTH) AF: 0.00547 AC: 127 AN: 23208

GnomAD4 genome AF: 0.0178 AC: 2714 AN: 152126 Hom.: 80 Cov.: 33 AF XY: 0.0177 AC XY: 1317 AN XY: 74368

African (AFR) AF: 0.0620 AC: 2576 AN: 41522

American (AMR) AF: 0.00603 AC: 92 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67968

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0152 Hom.: 11

Bravo AF: 0.0201

Asia WGS AF: 0.00347 AC: 12 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of butyrylcholinesterase Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.31
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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: rs139885577; hg19: chr3-165490990;