16-55819578-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001025195.2(CES1):c.863G>T(p.Arg288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 1 hom. )

Consequence

CES1
NM_001025195.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

CES1 (HGNC:1863): (carboxylesterase 1) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

CES1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2 link	c.863G>T	p.Arg288Leu	missense_variant	Exon 7 of 14	ENST00000360526.8	NP_001020366.1	P23141-2
CES1	NM_001025194.2 link	c.860G>T	p.Arg287Leu	missense_variant	Exon 7 of 14		NP_001020365.1	P23141-1
CES1	NM_001266.5 link	c.860G>T	p.Arg287Leu	missense_variant	Exon 7 of 14		NP_001257.4	P23141-3
CES1	XM_005255774.3 link	c.863G>T	p.Arg288Leu	missense_variant	Exon 7 of 14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CES1	ENST00000360526.8 link	c.863G>T	p.Arg288Leu	missense_variant	Exon 7 of 14	1	NM_001025195.2	ENSP00000353720.4	P23141-2
CES1	ENST00000361503.8 link	c.860G>T	p.Arg287Leu	missense_variant	Exon 7 of 14	1		ENSP00000355193.4	P23141-1
CES1	ENST00000422046.6 link	c.860G>T	p.Arg287Leu	missense_variant	Exon 7 of 14	1		ENSP00000390492.2	P23141-3
CES1	ENST00000569260.1 link	n.2G>T		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000456865.1	H3BSU0

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251388

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.860G>T (p.R287L) alteration is located in exon 7 (coding exon 7) of the CES1 gene. This alteration results from a G to T substitution at nucleotide position 860, causing the arginine (R) at amino acid position 287 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.3

.;M;M

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.8

D;D;D

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.67

MutPred

0.83

.;Loss of phosphorylation at T290 (P = 0.057);Loss of phosphorylation at T290 (P = 0.057);

MVP

0.74

MPC

0.18

ClinPred

0.87

GERP RS

2.9

Varity_R

0.63

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over