9-133062063-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001807.6(CEL):c.61G>T(p.Ala21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00037 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEL NM_001807.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.23

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065977573).
• BP6: Variant 9-133062063-G-T is Benign according to our data. Variant chr9-133062063-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1200172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEL	NM_001807.6	c.61G>T	p.Ala21Ser	missense_variant	1/11	ENST00000372080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEL	ENST00000372080.8	c.61G>T	p.Ala21Ser	missense_variant	1/11	5	NM_001807.6	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 519 AN: 151350 Hom.: 3 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000601 AC: 89 AN: 148094 Hom.: 2 AF XY: 0.000469 AC XY: 37 AN XY: 78950

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000238

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000369 AC: 514 AN: 1392488 Hom.: 4 Cov.: 32 AF XY: 0.000327 AC XY: 224 AN XY: 685602

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.000787

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000465

Gnomad4 OTH exome AF: 0.000764

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00345 AC: 522 AN: 151462 Hom.: 3 Cov.: 30 AF XY: 0.00369 AC XY: 273 AN XY: 73938

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000591

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.000289 Hom.: 0

ExAC AF: 0.000405 AC: 18

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 10, 2018

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 01, 2020

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	0.70	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Benign	0.062	T
Sift4G	Benign	0.13	T
Vest4		0.13
MVP		0.84
MPC		0.47
ClinPred		0.027	T
GERP RS		5.0
gMVP		0.41

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: rs558100781; hg19: chr9-135937450;