Genetic Variant CES1:c.1171-33C>A (chr16-55810697-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001025195.2(CES1):c.1171-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,591,444 control chromosomes in the GnomAD database, including 500,839 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 0.77 ( 45158 hom., cov: 34)

Exomes 𝑓: 0.79 ( 455681 hom. )

Consequence

CES1
NM_001025195.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2 link	c.1171-33C>A	intron_variant	Intron 10 of 13	ENST00000360526.8	NP_001020366.1	P23141-2
CES1	NM_001025194.2 link	c.1168-33C>A	intron_variant	Intron 10 of 13		NP_001020365.1	P23141-1
CES1	NM_001266.5 link	c.1165-33C>A	intron_variant	Intron 10 of 13		NP_001257.4	P23141-3
CES1	XM_005255774.3 link	c.1168-33C>A	intron_variant	Intron 10 of 13		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8 link	c.1171-33C>A		intron_variant	Intron 10 of 13	1	NM_001025195.2	ENSP00000353720.4		P23141-2

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

115961

AN:

150772

Hom.:

45117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.752

GnomAD3 exomes

AF:

0.732

AC:

182802

AN:

249766

Hom.:

68597

AF XY:

0.729

AC XY:

98482

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.758

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.776

Gnomad EAS exome

AF:

0.405

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.805

Gnomad NFE exome

AF:

0.813

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.789

AC:

1136927

AN:

1440552

Hom.:

455681

Cov.:

AF XY:

0.783

AC XY:

561852

AN XY:

717270

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.696

Gnomad4 ASJ exome

AF:

0.779

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.599

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.824

Gnomad4 OTH exome

AF:

0.763

GnomAD4 genome

AF:

0.769

AC:

116047

AN:

150892

Hom.:

45158

Cov.:

AF XY:

0.763

AC XY:

56268

AN XY:

73710

show subpopulations

Gnomad4 AFR

AF:

0.755

Gnomad4 AMR

AF:

0.762

Gnomad4 ASJ

AF:

0.770

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.802

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.752

Alfa

AF:

0.794

Hom.:

56020

Bravo

AF:

0.762

Asia WGS

AF:

0.512

AC:

1783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.21

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over