Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001807.6(CEL):c.2064C>G(p.Gly688Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0049 ( 9 hom. )

Failed GnomAD Quality Control

Consequence

CEL
NM_001807.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.330

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

maturity-onset diabetes of the young type 8
Inheritance: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CEL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-133071566-C-G is Benign according to our data. Variant chr9-133071566-C-G is described in ClinVar as Benign. ClinVar VariationId is 128690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.33 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001807.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	NM_001807.6	MANE Select	c.2064C>G	p.Gly688Gly	synonymous	Exon 11 of 11	NP_001798.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	ENST00000372080.8	TSL:5 MANE Select	c.2064C>G	p.Gly688Gly	synonymous	Exon 11 of 11	ENSP00000361151.6

Frequencies

GnomAD3 genomes

AF:

0.00835

AC:

316

AN:

37866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00692

Gnomad AMI

AF:

0.00758

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0224

Gnomad EAS

AF:

0.00744

Gnomad SAS

AF:

0.00154

Gnomad FIN

AF:

0.00711

Gnomad MID

AF:

0.0217

Gnomad NFE

AF:

0.00844

Gnomad OTH

AF:

0.0132

GnomAD2 exomes

AF:

0.00451

AC:

298

AN:

66008

AF XY:

0.00509

show subpopulations

Gnomad AFR exome

AF:

0.000821

Gnomad AMR exome

AF:

0.00418

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.00306

Gnomad FIN exome

AF:

0.00874

Gnomad NFE exome

AF:

0.00639

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00492

AC:

2562

AN:

520650

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

1346

AN XY:

268290

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00207

AC:

AN:

16390

American (AMR)

AF:

0.00386

AC:

AN:

16304

Ashkenazi Jewish (ASJ)

AF:

0.00891

AC:

AN:

9766

East Asian (EAS)

AF:

0.00252

AC:

AN:

17442

South Asian (SAS)

AF:

0.00132

AC:

AN:

56916

European-Finnish (FIN)

AF:

0.00482

AC:

AN:

13680

Middle Eastern (MID)

AF:

0.00359

AC:

AN:

1670

European-Non Finnish (NFE)

AF:

0.00576

AC:

2107

AN:

365754

Other (OTH)

AF:

0.00352

AC:

AN:

22728

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.331

Heterozygous variant carriers

173

346

520

693

866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00834

AC:

316

AN:

37878

Hom.:

Cov.:

AF XY:

0.00879

AC XY:

163

AN XY:

18546

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00699

AC:

AN:

12586

American (AMR)

AF:

0.0126

AC:

AN:

3172

Ashkenazi Jewish (ASJ)

AF:

0.0224

AC:

AN:

848

East Asian (EAS)

AF:

0.00679

AC:

AN:

1472

South Asian (SAS)

AF:

0.00155

AC:

AN:

1288

European-Finnish (FIN)

AF:

0.00711

AC:

AN:

1406

Middle Eastern (MID)

AF:

0.0217

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00844

AC:

139

AN:

16474

Other (OTH)

AF:

0.0132

AC:

AN:

454

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.316

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.92

(source)

DANN

Benign

0.63

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over