Genetic Variant NM_001365405.1:c.451C>A (chr16-66940249-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365405.1(CES2):c.451C>A(p.Leu151Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L151F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CES2
NM_001365405.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

0 publications found

Variant links:

Genes affected

CES2 (HGNC:1864): (carboxylesterase 2) 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. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

CES2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23589116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CES2	NM_001365405.1	MANE Select	c.451C>A	p.Leu151Ile	missense	Exon 4 of 12	NP_001352334.1	O00748-1
CES2	NM_003869.6		c.451C>A	p.Leu151Ile	missense	Exon 4 of 12	NP_003860.3
CES2	NM_198061.3		c.451C>A	p.Leu151Ile	missense	Exon 4 of 12	NP_932327.2	O00748-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CES2	ENST00000317091.10	TSL:1 MANE Select	c.451C>A	p.Leu151Ile	missense	Exon 4 of 12	ENSP00000317842.5	O00748-1
CES2	ENST00000417689.6	TSL:1	c.451C>A	p.Leu151Ile	missense	Exon 4 of 12	ENSP00000394452.2	O00748-2
CES2	ENST00000971765.1		c.745C>A	p.Leu249Ile	missense	Exon 4 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248306

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705998

show subpopulations

African (AFR)

AF:

0.0000313

AC:

AN:

31910

American (AMR)

AF:

0.00

AC:

AN:

42466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25186

East Asian (EAS)

AF:

0.00

AC:

AN:

37710

South Asian (SAS)

AF:

0.00

AC:

AN:

78736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090086

Other (OTH)

AF:

0.00

AC:

AN:

58496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.46

PhyloP100

0.19

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

REVEL

Benign

0.23

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Vest4

0.47

MVP

0.15

MPC

0.67

ClinPred

0.37

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over