9-133065052-T-G

Variant names:

• chr9-133065052-T-G
• rs113056079
• NM_001807.6:c.353T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001807.6(CEL):​c.353T>G​(p.Leu118Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00318 in 1,612,998 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (64 hom.)
• Consequence: CEL NM_001807.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.88
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013227224).
• BP6: Variant 9-133065052-T-G is Benign according to our data. Variant chr9-133065052-T-G is described in ClinVar as Benign. ClinVar VariationId is 128684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

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.353T>G	p.Leu118Arg	missense	Exon 4 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.353T>G	p.Leu118Arg	missense	Exon 4 of 11	ENSP00000361151.6

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2411 AN: 151940 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00438 AC: 1087 AN: 248422 AF XY: 0.00341

Gnomad AFR exome AF: 0.0528

Gnomad AMR exome AF: 0.00568

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000508

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00186 AC: 2712 AN: 1460940 Hom.: 64 Cov.: 32 AF XY: 0.00163 AC XY: 1188 AN XY: 726774

African (AFR) AF: 0.0523 AC: 1751 AN: 33464

American (AMR) AF: 0.00601 AC: 269 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86248

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52738

Middle Eastern (MID) AF: 0.00611 AC: 34 AN: 5566

European-Non Finnish (NFE) AF: 0.000323 AC: 359 AN: 1111992

Other (OTH) AF: 0.00470 AC: 284 AN: 60372

GnomAD4 genome AF: 0.0159 AC: 2416 AN: 152058 Hom.: 68 Cov.: 33 AF XY: 0.0156 AC XY: 1159 AN XY: 74332

African (AFR) AF: 0.0530 AC: 2194 AN: 41426

American (AMR) AF: 0.00974 AC: 149 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10592

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 67974

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00525 Hom.: 51

Bravo AF: 0.0186

ESP6500AA AF: 0.0507 AC: 194

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.00502 AC: 606

EpiCase AF: 0.000436

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32041611)

Dec 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

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

Mar 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Maturity-onset diabetes of the young type 8 Benign:1

Jul 12, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Monogenic diabetes Benign:1

Nov 09, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG criteria: BS2 (185 controls and 185 cases in T2DM), BA1 (5% in gnomAD African)= benign (REVEL 0.479 + BP4/4 predictors +PP3/6 predictors= conflicting evidence, not using)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.81	T
PhyloP100		5.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.48
Sift	Benign	0.083	T
Sift4G	Benign	0.12	T
Vest4		0.88
MVP		0.86
MPC		1.4
ClinPred		0.023	T
GERP RS		5.2
gMVP		0.93
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs113056079; hg19: chr9-135940439;