Genetic Variant CEL:p.Pro570Pro (chr9-133071212-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_001807.6(CEL):c.1710C>T(p.Pro570Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,117,868 control chromosomes in the GnomAD database, including 25,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5582 hom., cov: 29)

Exomes 𝑓: 0.13 ( 19784 hom. )

Consequence

CEL
NM_001807.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.46

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:

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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=-0.79).

BP6

Variant 9-133071212-C-T is Benign according to our data. Variant chr9-133071212-C-T is described in ClinVar as [Benign]. Clinvar id is 128685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEL	NM_001807.6 link	c.1710C>T	p.Pro570Pro	synonymous_variant	Exon 11 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.1710C>T	p.Pro570Pro	synonymous_variant	Exon 11 of 11	5	NM_001807.6	ENSP00000361151.6		P19835-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

37426

AN:

147170

Hom.:

5575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.230

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.110

AC:

17191

AN:

156926

Hom.:

2616

AF XY:

0.0991

AC XY:

8545

AN XY:

86226

show subpopulations

Gnomad AFR exome

AF:

0.0783

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.0871

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.0201

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.135

AC:

130647

AN:

970590

Hom.:

19784

Cov.:

AF XY:

0.138

AC XY:

68357

AN XY:

495092

show subpopulations

Gnomad4 AFR exome

AF:

0.0706

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.0554

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.254

AC:

37459

AN:

147278

Hom.:

5582

Cov.:

AF XY:

0.255

AC XY:

18363

AN XY:

71874

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.0936

Gnomad4 FIN

AF:

0.381

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.226

Hom.:

880

Bravo

AF:

0.247

Asia WGS

AF:

0.100

AC:

334

AN:

3314

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.14

DANN

Benign

0.74

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