rs145327297

Variant names:

• chr3-165773243-A-T
• rs145327297
• NM_000055.4:c.*139T>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_000055.4(BCHE):​c.*139T>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 0.00193 in 748,234 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00087 (2 hom.)
• Consequence: BCHE NM_000055.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.08
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00609 (927/152280) while in subpopulation AFR AF = 0.0203 (842/41576). AF 95% confidence interval is 0.0191. There are 6 homozygotes in GnomAd4. There are 384 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 6 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	NM_000055.4	MANE Select	c.*139T>A		3_prime_UTR	Exon 4 of 4	NP_000046.1	P06276
	BCHE	NR_137635.2		n.541T>A		non_coding_transcript_exon	Exon 3 of 3
	BCHE	NR_137636.2		n.2145T>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCHE	ENST00000264381.8	TSL:1 MANE Select	c.*139T>A		3_prime_UTR	Exon 4 of 4	ENSP00000264381.3	P06276
	BCHE	ENST00000479451.5	TSL:1	c.*139T>A		3_prime_UTR	Exon 3 of 3	ENSP00000418325.1	H0Y885
	BCHE	ENST00000855337.1		c.*139T>A		3_prime_UTR	Exon 5 of 5	ENSP00000525396.1

Frequencies

GnomAD3 genomes AF: 0.00607 AC: 924 AN: 152162 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000866 AC: 516 AN: 595954 Hom.: 2 Cov.: 8 AF XY: 0.000748 AC XY: 232 AN XY: 310354

African (AFR) AF: 0.0211 AC: 314 AN: 14884

American (AMR) AF: 0.00226 AC: 44 AN: 19502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15478

East Asian (EAS) AF: 0.00 AC: 0 AN: 31000

South Asian (SAS) AF: 0.000105 AC: 5 AN: 47694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34862

Middle Eastern (MID) AF: 0.00308 AC: 7 AN: 2274

European-Non Finnish (NFE) AF: 0.000238 AC: 95 AN: 399750

Other (OTH) AF: 0.00167 AC: 51 AN: 30510

GnomAD4 genome AF: 0.00609 AC: 927 AN: 152280 Hom.: 6 Cov.: 33 AF XY: 0.00516 AC XY: 384 AN XY: 74460

African (AFR) AF: 0.0203 AC: 842 AN: 41576

American (AMR) AF: 0.00314 AC: 48 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68008

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00583 Hom.: 0

Bravo AF: 0.00707

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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	-0.76
CADD	Benign	4.0
DANN	Benign	0.63
PhyloP100		2.1
Mutation Taster		=99/1	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: rs145327297; hg19: chr3-165491031;