9-133062009-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001807.6(CEL):c.7C>T(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,549,678 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (16 hom.)
• Consequence: CEL NM_001807.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.86

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061931014).
• BP6: Variant 9-133062009-C-T is Benign according to our data. Variant chr9-133062009-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 218596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133062009-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00609 (925/151926) while in subpopulation AFR AF= 0.0188 (777/41268). AF 95% confidence interval is 0.0177. There are 4 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 913 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEL	NM_001807.6	c.7C>T	p.Arg3Cys	missense_variant	1/11	ENST00000372080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEL	ENST00000372080.8	c.7C>T	p.Arg3Cys	missense_variant	1/11	5	NM_001807.6	P1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 913 AN: 151808 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00243 AC: 375 AN: 154382 Hom.: 5 AF XY: 0.00186 AC XY: 153 AN XY: 82042

Gnomad AFR exome AF: 0.0226

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.00260

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000264

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00485

GnomAD4 exome AF: 0.00160 AC: 2241 AN: 1397752 Hom.: 16 Cov.: 32 AF XY: 0.00146 AC XY: 1008 AN XY: 689112

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.00359

Gnomad4 ASJ exome AF: 0.00195

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.0000204

Gnomad4 NFE exome AF: 0.000966

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.00609 AC: 925 AN: 151926 Hom.: 4 Cov.: 30 AF XY: 0.00572 AC XY: 425 AN XY: 74280

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.00452

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00151 Hom.: 0

ESP6500AA AF: 0.0123 AC: 43

ESP6500EA AF: 0.00103 AC: 8

ExAC AF: 0.00108 AC: 97

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	This variant is associated with the following publications: (PMID: 32041611) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CEL: BP4, BS1, BS2 -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 10, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jul 09, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.57	T
MutationTaster	Benign	0.92	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.028	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.33
MVP		0.84
MPC		1.2
ClinPred		0.017	T
GERP RS		4.8
gMVP		0.67

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

Other links and lift over

dbSNP: rs201383133; hg19: chr9-135937396; COSMIC: COSV99053334; COSMIC: COSV99053334;