rs77696629

Positions:

chr9-133070628-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001807.6(CEL):c.1454T>C(p.Ile485Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00906 in 1,436,658 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 10 hom., cov: 29)

Exomes 𝑓: 0.0077 ( 61 hom. )

Consequence

CEL
NM_001807.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.40

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=0.009507239).

BP6

Variant 9-133070628-T-C is Benign according to our data. Variant chr9-133070628-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 393421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133070628-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0259 (2742/105858) while in subpopulation AFR AF= 0.0454 (1318/29002). AF 95% confidence interval is 0.0434. There are 10 homozygotes in gnomad4. There are 1320 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2742 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEL	NM_001807.6 linkuse as main transcript	c.1454T>C	p.Ile485Thr	missense_variant	10/11	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.1454T>C	p.Ile485Thr	missense_variant	10/11	5	NM_001807.6	ENSP00000361151	P1	P19835-1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

2741

AN:

105760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.0105

Gnomad AMR

AF:

0.0249

Gnomad ASJ

AF:

0.00854

Gnomad EAS

AF:

0.0151

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0684

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0332

GnomAD4 exome

AF:

0.00772

AC:

10280

AN:

1330800

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

5442

AN XY:

654874

show subpopulations

Gnomad4 AFR exome

AF:

0.0208

Gnomad4 AMR exome

AF:

0.00703

Gnomad4 ASJ exome

AF:

0.00489

Gnomad4 EAS exome

AF:

0.00118

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00485

Gnomad4 NFE exome

AF:

0.00759

Gnomad4 OTH exome

AF:

0.00805

GnomAD4 genome

AF:

0.0259

AC:

2742

AN:

105858

Hom.:

Cov.:

AF XY:

0.0253

AC XY:

1320

AN XY:

52106

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.00854

Gnomad4 EAS

AF:

0.0149

Gnomad4 SAS

AF:

0.0275

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0329

Alfa

AF:

0.0619

Hom.:

ExAC

AF:

0.0194

AC:

2341

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 12, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Maturity-onset diabetes of the young type 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Monogenic diabetes

Benign:1

Benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Feb 08, 2019

ACMG criteria: BA1 (2.8% in gnomAD Africans and 1% in gnomAD ENF) (BP4/3 predictors + PP3/7 predictors + REVEL 0.615: conflicting evidence, not using both)= Benign -

Transitory neonatal diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

CEL gene mutations are associated with MODY and neonatal diabetes. rs77696629 of CEL gene plays a role in increasing the risk of chronic pancreatitis. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.37

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.61

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Vest4

0.35

MPC

1.0

ClinPred

0.014

GERP RS

4.6

gMVP

0.73

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