dbSNP rs3815583: CES1:c.-75T>G (chr16-55833130-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000361503.8(CES1):c.-75T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,238,702 control chromosomes in the GnomAD database, including 21,825 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 0.23 ( 3207 hom., cov: 34)

Exomes 𝑓: 0.14 ( 18618 hom. )

Consequence

CES1
ENST00000361503.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.13

Publications

29 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CES1	NM_001025195.2 link	c.-75T>G	upstream_gene_variant	ENST00000360526.8	NP_001020366.1	P23141-2
CES1	NM_001025194.2 link	c.-75T>G	upstream_gene_variant		NP_001020365.1	P23141-1
CES1	NM_001266.5 link	c.-75T>G	upstream_gene_variant		NP_001257.4	P23141-3
CES1	XM_005255774.3 link	c.-75T>G	upstream_gene_variant		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8 link	c.-75T>G		upstream_gene_variant		1	NM_001025195.2	ENSP00000353720.4		P23141-2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

33809

AN:

148356

Hom.:

3202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.143

AC:

156360

AN:

1090234

Hom.:

18618

Cov.:

AF XY:

0.145

AC XY:

79911

AN XY:

550250

show subpopulations

African (AFR)

AF:

0.225

AC:

5782

AN:

25702

American (AMR)

AF:

0.231

AC:

9461

AN:

40968

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

2828

AN:

22516

East Asian (EAS)

AF:

0.417

AC:

12789

AN:

30702

South Asian (SAS)

AF:

0.199

AC:

13687

AN:

68830

European-Finnish (FIN)

AF:

0.128

AC:

6167

AN:

48112

Middle Eastern (MID)

AF:

0.186

AC:

849

AN:

4574

European-Non Finnish (NFE)

AF:

0.122

AC:

97597

AN:

802088

Other (OTH)

AF:

0.154

AC:

7200

AN:

46742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5019

10038

15058

20077

25096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.228

AC:

33822

AN:

148468

Hom.:

3207

Cov.:

AF XY:

0.228

AC XY:

16528

AN XY:

72498

show subpopulations

African (AFR)

AF:

0.283

AC:

11530

AN:

40756

American (AMR)

AF:

0.230

AC:

3453

AN:

14992

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

610

AN:

3416

East Asian (EAS)

AF:

0.421

AC:

2061

AN:

4894

South Asian (SAS)

AF:

0.253

AC:

1177

AN:

4650

European-Finnish (FIN)

AF:

0.163

AC:

1677

AN:

10302

Middle Eastern (MID)

AF:

0.225

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.191

AC:

12658

AN:

66230

Other (OTH)

AF:

0.217

AC:

446

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

940

1880

2819

3759

4699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.218

Hom.:

280

Asia WGS

AF:

0.341

AC:

1186

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.032

(source)

DANN

Benign

0.23

PhyloP100

-3.1

PromoterAI

0.073

Neutral

(source)

Mutation Taster

=299/1

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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rs3815583

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