dbSNP rs587780309: CEL:p.Ala656Thr (chr9-133071468-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001807.6(CEL):c.1966G>A(p.Ala656Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A656P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 6)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEL
NM_001807.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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: 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19546485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEL	NM_001807.6 link	c.1966G>A	p.Ala656Thr	missense_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.1966G>A	p.Ala656Thr	missense_variant	Exon 11 of 11	5	NM_001807.6	ENSP00000361151.6		P19835-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

113922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62426

African (AFR)

AF:

0.00

AC:

AN:

2396

American (AMR)

AF:

0.00

AC:

AN:

1566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1868

East Asian (EAS)

AF:

0.00

AC:

AN:

5726

South Asian (SAS)

AF:

0.00

AC:

AN:

9696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

420

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

80132

Other (OTH)

AF:

0.00

AC:

AN:

5550

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.68

PhyloP100

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.27

REVEL

Benign

0.15

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.011

Vest4

0.18

MVP

0.67

MPC

0.80

ClinPred

0.64

GERP RS

0.65

gMVP

0.044

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over