Variant 16-55846598-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001143685.2(CES5A):c.1581C>T(p.Leu527=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,614,106 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 33 hom., cov: 31)

Exomes 𝑓: 0.0059 ( 166 hom. )

Consequence

CES5A
NM_001143685.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

CES5A (HGNC:26459): (carboxylesterase 5A) 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 CES5, is predominantly expressed in peripheral tissues, including brain, kidney, lung and testis. It encodes a secreted enzyme. Because of high levels in the urine of male domestic cats, this enzyme is also called cauxin (carboxylesterase-like urinary excreted protein). The enzyme functions in regulating the production of a pheromone precursor and may contribute to lipid and cholesterol transfer processes within male reproductive fluids. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

CES5A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-55846598-G-A is Benign according to our data. Variant chr16-55846598-G-A is described in ClinVar as [Benign]. Clinvar id is 770631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CES5A	NM_001143685.2 linkuse as main transcript	c.1581C>T	p.Leu527=	synonymous_variant	13/13	ENST00000290567.14	NP_001137157.1
CES5A	NM_001190158.1 linkuse as main transcript	c.1668C>T	p.Leu556=	synonymous_variant	14/14		NP_001177087.1
CES5A	NM_145024.3 linkuse as main transcript	c.1431C>T	p.Leu477=	synonymous_variant	12/12		NP_659461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES5A	ENST00000290567.14 linkuse as main transcript	c.1581C>T	p.Leu527=	synonymous_variant	13/13	1	NM_001143685.2	ENSP00000290567	P2	Q6NT32-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2173

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0349

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.00561

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00987

AC:

2481

AN:

251490

Hom.:

AF XY:

0.00910

AC XY:

1237

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.00960

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.0247

Gnomad SAS exome

AF:

0.00611

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00370

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.00595

AC:

8697

AN:

1461882

Hom.:

166

Cov.:

AF XY:

0.00593

AC XY:

4313

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0383

Gnomad4 EAS exome

AF:

0.0521

Gnomad4 SAS exome

AF:

0.00550

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.0143

AC:

2177

AN:

152224

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1025

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0348

Gnomad4 AMR

AF:

0.00955

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00810

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.32

DANN

Benign

0.57

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over