dbSNP rs12149371: CES1:c.-39A>T (chr16-55833094-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025195.2(CES1):c.-39A>T 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 0.0000062 in 1,452,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

CES1
NM_001025195.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.59

Publications

9 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2 link	c.-39A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	ENST00000360526.8	NP_001020366.1	P23141-2
CES1	NM_001025195.2 link	c.-39A>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000360526.8	NP_001020366.1	P23141-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8 link	c.-39A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14	1	NM_001025195.2	ENSP00000353720.4		P23141-2
CES1	ENST00000360526.8 link	c.-39A>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_001025195.2	ENSP00000353720.4		P23141-2

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143630

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000312

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000466

AC:

AN:

214430

AF XY:

0.00000860

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000535

AC:

AN:

1308498

Hom.:

Cov.:

AF XY:

0.00000459

AC XY:

AN XY:

653206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30512

American (AMR)

AF:

0.00

AC:

AN:

42890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24380

East Asian (EAS)

AF:

0.00

AC:

AN:

34232

South Asian (SAS)

AF:

0.00

AC:

AN:

79074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5056

European-Non Finnish (NFE)

AF:

0.00000708

AC:

AN:

988334

Other (OTH)

AF:

0.00

AC:

AN:

54448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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

AF:

0.0000139

AC:

AN:

143630

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39538

American (AMR)

AF:

0.00

AC:

AN:

14416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3304

East Asian (EAS)

AF:

0.00

AC:

AN:

4734

South Asian (SAS)

AF:

0.00

AC:

AN:

4428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000312

AC:

AN:

64174

Other (OTH)

AF:

0.00

AC:

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.750

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:

0.00

Hom.:

252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.010

(source)

DANN

Benign

0.33

PhyloP100

-4.6

PromoterAI

-0.028

Neutral

(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