9-133065052-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001807.6(CEL):c.353T>G(p.Leu118Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00318 in 1,612,998 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 68 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 64 hom. )

Consequence

CEL
NM_001807.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.88

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013227224).

BP6

Variant 9-133065052-T-G is Benign according to our data. Variant chr9-133065052-T-G is described in ClinVar as [Benign]. Clinvar id is 128684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133065052-T-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEL	NM_001807.6 link	c.353T>G	p.Leu118Arg	missense_variant	Exon 4 of 11	ENST00000372080.8	NP_001798.3	B4DSX9Q86SR3O75612

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEL	ENST00000372080.8 link	c.353T>G	p.Leu118Arg	missense_variant	Exon 4 of 11	5	NM_001807.6	ENSP00000361151.6		P19835-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2411

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00438

AC:

1087

AN:

248422

Hom.:

AF XY:

0.00341

AC XY:

460

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.0528

Gnomad AMR exome

AF:

0.00568

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000508

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00186

AC:

2712

AN:

1460940

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1188

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0523

Gnomad4 AMR exome

AF:

0.00601

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000323

Gnomad4 OTH exome

AF:

0.00470

GnomAD4 genome

AF:

0.0159

AC:

2416

AN:

152058

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0530

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.0186

ESP6500AA

AF:

0.0507

AC:

194

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.00502

AC:

606

EpiCase

AF:

0.000436

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32041611) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Maturity-onset diabetes of the young type 8

Benign:1

Jul 12, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Monogenic diabetes

Benign:1

Nov 09, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG criteria: BS2 (185 controls and 185 cases in T2DM), BA1 (5% in gnomAD African)= benign (REVEL 0.479 + BP4/4 predictors +PP3/6 predictors= conflicting evidence, not using) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.81

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.48

Sift

Benign

0.083

Sift4G

Benign

0.12

Vest4

0.88

MVP

0.86

MPC

1.4

ClinPred

0.023

GERP RS

5.2

gMVP

0.93

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