Variant rs3848290 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001364782.1(CES4A):c.1357G>A(p.Ala453Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,536,428 control chromosomes in the GnomAD database, including 2,673 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.078 ( 1453 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1220 hom. )

Consequence

CES4A
NM_001364782.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Variant links:

Genes affected

CES4A (HGNC:26741): (carboxylesterase 4A) 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 also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES6, encodes a secreted enzyme, and may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2010]

CES4A 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 (MetaRNN=0.0046688616).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES4A	NM_001364782.1 linkuse as main transcript	c.1357G>A	p.Ala453Thr	missense_variant	12/14	ENST00000648724.3	NP_001351711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES4A	ENST00000648724.3 linkuse as main transcript	c.1357G>A	p.Ala453Thr	missense_variant	12/14		NM_001364782.1	ENSP00000497868	P1	Q5XG92-1

Frequencies

GnomAD3 genomes

AF:

0.0783

AC:

11907

AN:

152024

Hom.:

1452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00453

Gnomad OTH

AF:

0.0570

GnomAD3 exomes

AF:

0.0195

AC:

2714

AN:

139408

Hom.:

254

AF XY:

0.0152

AC XY:

1139

AN XY:

75144

show subpopulations

Gnomad AFR exome

AF:

0.274

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0105

AC:

14560

AN:

1384286

Hom.:

1220

Cov.:

AF XY:

0.00950

AC XY:

6489

AN XY:

683068

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0175

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.000322

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.0210

GnomAD4 genome

AF:

0.0784

AC:

11925

AN:

152142

Hom.:

1453

Cov.:

AF XY:

0.0760

AC XY:

5651

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00454

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0149

Hom.:

326

Bravo

AF:

0.0884

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00337

AC:

ExAC

AF:

0.0140

AC:

466

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.44

DANN

Benign

0.97

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.39

.;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PROVEAN

Benign

-0.30

.;N

REVEL

Benign

0.040

Sift

Benign

0.041

.;D

Sift4G

Uncertain

0.0060

.;D

Vest4

0.018

ClinPred

0.0020

GERP RS

-1.9

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