Variant 9-133071468-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001807.6(CEL):c.1966G>C(p.Ala656Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 6)

Exomes 𝑓: 0.0042 ( 18 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: 1.01

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014160126).

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEL	NM_001807.6 linkuse as main transcript	c.1966G>C	p.Ala656Pro	missense_variant	11/11	ENST00000372080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEL	ENST00000372080.8 linkuse as main transcript	c.1966G>C	p.Ala656Pro	missense_variant	11/11	5	NM_001807.6	P1	P19835-1

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

AN:

48350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00556

Gnomad AMR

AF:

0.00123

Gnomad ASJ

AF:

0.00948

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00488

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00247

Gnomad OTH

AF:

0.00154

GnomAD3 exomes

AF:

0.000644

AC:

AN:

3104

Hom.:

AF XY:

0.000482

AC XY:

AN XY:

2074

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00415

AC:

473

AN:

113892

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

297

AN XY:

62406

show subpopulations

Gnomad4 AFR exome

AF:

0.000835

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.000349

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.00533

Gnomad4 NFE exome

AF:

0.00292

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.00174

AC:

AN:

48336

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

AN XY:

22976

show subpopulations

Gnomad4 AFR

AF:

0.000196

Gnomad4 AMR

AF:

0.00123

Gnomad4 ASJ

AF:

0.00948

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00493

Gnomad4 FIN

AF:

0.00181

Gnomad4 NFE

AF:

0.00247

Gnomad4 OTH

AF:

0.00155

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autoimmunity;C0011849:Diabetes mellitus;C0011854:Diabetes mellitus type 1;C0017152:Gastritis;C0017658:Glomerulonephritis;C0040147:Thyroiditis;C0085695:Chronic gastritis;C0403416:Crescentic glomerulonephritis;C0443147:Autosomal dominant inheritance;C1561643:Chronic kidney disease;C1847879:X-linked dominant inheritance

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Personalized Medicine, Children's Hospital Los Angeles

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 24, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.75

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.060

REVEL

Benign

0.17

Sift

Uncertain

0.010

Sift4G

Uncertain

0.014

Vest4

0.22

MVP

0.56

MPC

0.98

ClinPred

0.099

GERP RS

0.65

gMVP

0.046

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