Variant rs587780310 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001807.6(CEL):c.2092T>G(p.Ser698Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 15)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEL
NM_001807.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.348

Variant links:

Genes affected

CEL (HGNC:1848): (carboxyl ester lipase) The protein encoded by this gene is a glycoprotein secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk. The physiological role of this protein is in cholesterol and lipid-soluble vitamin ester hydrolysis and absorption. This encoded protein promotes large chylomicron production in the intestine. Also its presence in plasma suggests its interactions with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis. In pancreatic tumoral cells, this encoded protein is thought to be sequestrated within the Golgi compartment and is probably not secreted. This gene contains a variable number of tandem repeat (VNTR) polymorphism in the coding region that may influence the function of the encoded protein. [provided by RefSeq, Jul 2008]

CEL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07587674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEL	NM_001807.6 linkuse as main transcript	c.2092T>G	p.Ser698Ala	missense_variant	11/11	ENST00000372080.8	NP_001798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEL	ENST00000372080.8 linkuse as main transcript	c.2092T>G	p.Ser698Ala	missense_variant	11/11	5	NM_001807.6	ENSP00000361151	P1	P19835-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

85692

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.000907

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000925

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000922

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.0000978

AC:

AN:

143100

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

79182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000843

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000142

AC:

167

AN:

1177344

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

587460

show subpopulations

Gnomad4 AFR exome

AF:

0.0000355

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.0000305

Gnomad4 SAS exome

AF:

0.0000261

Gnomad4 FIN exome

AF:

0.0000920

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000723

AC:

AN:

85756

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

AN XY:

41542

show subpopulations

Gnomad4 AFR

AF:

0.000331

Gnomad4 AMR

AF:

0.00106

Gnomad4 ASJ

AF:

0.000907

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000925

Gnomad4 NFE

AF:

0.000922

Gnomad4 OTH

AF:

0.00264

Alfa

AF:

0.00236

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Maturity-onset diabetes of the young type 8

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 17, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.012

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.020

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.19

MVP

0.66

MPC

0.66

ClinPred

0.19

GERP RS

-2.1

gMVP

0.037

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