Genetic Variant CES2:c.915+70C>T (chr16-66941292-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001365405.1(CES2):c.915+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,579,010 control chromosomes in the GnomAD database, including 255 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 0.014 ( 26 hom., cov: 33)

Exomes 𝑓: 0.016 ( 229 hom. )

Consequence

CES2
NM_001365405.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0141 (2151/152312) while in subpopulation NFE AF = 0.0214 (1454/68018). AF 95% confidence interval is 0.0205. There are 26 homozygotes in GnomAd4. There are 1041 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES2	NM_001365405.1 link	c.915+70C>T		intron_variant	Intron 6 of 11	ENST00000317091.10	NP_001352334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES2	ENST00000317091.10 link	c.915+70C>T		intron_variant	Intron 6 of 11	1	NM_001365405.1	ENSP00000317842.5		O00748-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2153

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.0163

AC:

23187

AN:

1426698

Hom.:

229

Cov.:

AF XY:

0.0161

AC XY:

11350

AN XY:

706810

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

32760

American (AMR)

AF:

0.00939

AC:

374

AN:

39812

Ashkenazi Jewish (ASJ)

AF:

0.00500

AC:

123

AN:

24624

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38300

South Asian (SAS)

AF:

0.00294

AC:

238

AN:

81018

European-Finnish (FIN)

AF:

0.0247

AC:

1259

AN:

50958

Middle Eastern (MID)

AF:

0.00143

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.0185

AC:

20239

AN:

1094556

Other (OTH)

AF:

0.0145

AC:

856

AN:

59056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1237

2473

3710

4946

6183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

686

1372

2058

2744

3430

<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:

0.0141

AC:

2151

AN:

152312

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1041

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00339

AC:

141

AN:

41562

American (AMR)

AF:

0.0159

AC:

243

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0239

AC:

254

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0214

AC:

1454

AN:

68018

Other (OTH)

AF:

0.0118

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0191

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

(source)

DANN

Benign

0.52

PhyloP100

-0.24

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over