dbSNP rs11075646: CES2:c.-363C>G (chr16-66935273-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000417689.6(CES2):c.-363C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 674,068 control chromosomes in the GnomAD database, including 4,338 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 0.14 ( 2032 hom., cov: 32)

Exomes 𝑓: 0.083 ( 2306 hom. )

Consequence

CES2
ENST00000417689.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

21 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES2	NM_001365405.1 link	c.-363C>G		upstream_gene_variant		ENST00000317091.10	NP_001352334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES2	ENST00000317091.10 link	c.-363C>G		upstream_gene_variant		1	NM_001365405.1	ENSP00000317842.5		O00748-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20683

AN:

151940

Hom.:

2026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0344

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.0833

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0826

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.0835

AC:

43562

AN:

522010

Hom.:

2306

Cov.:

AF XY:

0.0817

AC XY:

22207

AN XY:

271656

show subpopulations

African (AFR)

AF:

0.272

AC:

3870

AN:

14224

American (AMR)

AF:

0.0652

AC:

1439

AN:

22056

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

1867

AN:

13626

East Asian (EAS)

AF:

0.0232

AC:

760

AN:

32796

South Asian (SAS)

AF:

0.0652

AC:

2649

AN:

40644

European-Finnish (FIN)

AF:

0.0927

AC:

3167

AN:

34168

Middle Eastern (MID)

AF:

0.0854

AC:

236

AN:

2762

European-Non Finnish (NFE)

AF:

0.0804

AC:

26823

AN:

333754

Other (OTH)

AF:

0.0983

AC:

2751

AN:

27980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1983

3966

5950

7933

9916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.136

AC:

20720

AN:

152058

Hom.:

2032

Cov.:

AF XY:

0.133

AC XY:

9859

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.280

AC:

11605

AN:

41396

American (AMR)

AF:

0.0877

AC:

1340

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3470

East Asian (EAS)

AF:

0.0347

AC:

179

AN:

5164

South Asian (SAS)

AF:

0.0651

AC:

314

AN:

4820

European-Finnish (FIN)

AF:

0.0833

AC:

884

AN:

10612

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0826

AC:

5614

AN:

67996

Other (OTH)

AF:

0.125

AC:

263

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

848

1696

2545

3393

4241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.114

Hom.:

185

Bravo

AF:

0.141

Asia WGS

AF:

0.0890

AC:

312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

(source)

DANN

Benign

0.67

PhyloP100

-1.0

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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