rs587780309

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A656A) has been classified as Likely benign.

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

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 1.01

Publications

6 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: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen
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 -9 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00174 (84/48336) while in subpopulation SAS AF = 0.00493 (8/1622). AF 95% confidence interval is 0.00245. There are 0 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 6. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 84 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	NM_001807.6	MANE Select	c.1966G>C	p.Ala656Pro	missense	Exon 11 of 11	NP_001798.3	P19835-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	ENST00000372080.8	TSL:5 MANE Select	c.1966G>C	p.Ala656Pro	missense	Exon 11 of 11	ENSP00000361151.6	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

GnomAD2 exomes

AF:

0.000644

AC:

AN:

3104

AF XY:

0.000482

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 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

African (AFR)

AF:

0.000835

AC:

AN:

2396

American (AMR)

AF:

0.00128

AC:

AN:

1566

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

AN:

1868

East Asian (EAS)

AF:

0.000349

AC:

AN:

5726

South Asian (SAS)

AF:

0.0165

AC:

160

AN:

9692

European-Finnish (FIN)

AF:

0.00533

AC:

AN:

6568

Middle Eastern (MID)

AF:

0.00714

AC:

AN:

420

European-Non Finnish (NFE)

AF:

0.00292

AC:

234

AN:

80110

Other (OTH)

AF:

0.00397

AC:

AN:

5546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00174

AC:

AN:

48336

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

AN XY:

22976

show subpopulations

African (AFR)

AF:

0.000196

AC:

AN:

15340

American (AMR)

AF:

0.00123

AC:

AN:

4884

Ashkenazi Jewish (ASJ)

AF:

0.00948

AC:

AN:

1160

East Asian (EAS)

AF:

0.00

AC:

AN:

2100

South Asian (SAS)

AF:

0.00493

AC:

AN:

1622

European-Finnish (FIN)

AF:

0.00181

AC:

AN:

1660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00247

AC:

AN:

20662

Other (OTH)

AF:

0.00155

AC:

AN:

646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

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

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Maturity-onset diabetes of the young (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

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

PhyloP100

1.0

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

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over