Genetic Variant NM_001365405.1:c.441C>T (chr16-66940239-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001365405.1(CES2):c.441C>T(p.His147His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,538,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

CES2
NM_001365405.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.66

Publications

1 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-66940239-C-T is Benign according to our data. Variant chr16-66940239-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2646608.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

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.441C>T	p.His147His	synonymous	Exon 4 of 12	NP_001352334.1	O00748-1
CES2	NM_003869.6		c.441C>T	p.His147His	synonymous	Exon 4 of 12	NP_003860.3
CES2	NM_198061.3		c.441C>T	p.His147His	synonymous	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.441C>T	p.His147His	synonymous	Exon 4 of 12	ENSP00000317842.5	O00748-1
CES2	ENST00000417689.6	TSL:1	c.441C>T	p.His147His	synonymous	Exon 4 of 12	ENSP00000394452.2	O00748-2
CES2	ENST00000971765.1		c.735C>T	p.His245His	synonymous	Exon 4 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

130030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000304

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00112

GnomAD2 exomes

AF:

0.0000759

AC:

AN:

250426

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000143

AC:

201

AN:

1408854

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

699218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31288

American (AMR)

AF:

0.000265

AC:

AN:

41432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24832

East Asian (EAS)

AF:

0.00

AC:

AN:

36682

South Asian (SAS)

AF:

0.00

AC:

AN:

76524

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.000169

AC:

183

AN:

1083360

Other (OTH)

AF:

0.000104

AC:

AN:

57826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000123

AC:

AN:

130144

Hom.:

Cov.:

AF XY:

0.0000783

AC XY:

AN XY:

63820

show subpopulations

African (AFR)

AF:

0.0000289

AC:

AN:

34648

American (AMR)

AF:

0.000304

AC:

AN:

13174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3042

East Asian (EAS)

AF:

0.00

AC:

AN:

4202

South Asian (SAS)

AF:

0.00

AC:

AN:

4030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

58950

Other (OTH)

AF:

0.00111

AC:

AN:

1802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.000132

EpiCase

AF:

0.000219

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.16

(source)

DANN

Benign

0.80

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over