9-133064283-A-C

Position:

• chr9-133064283-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001807.6(CEL):​c.67-121A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00822 in 1,345,208 control chromosomes in the GnomAD database, including 691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (401 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (290 hom.)
• Consequence: CEL NM_001807.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.603

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 (BayesDel_noAF=-0.88).
• BP6: Variant 9-133064283-A-C is Benign according to our data. Variant chr9-133064283-A-C is described in ClinVar as [Benign]. Clinvar id is 1267374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEL	NM_001807.6	c.67-121A>C		intron_variant		ENST00000372080.8	NP_001798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEL	ENST00000372080.8	c.67-121A>C		intron_variant		5	NM_001807.6	ENSP00000361151	P1

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5959 AN: 152108 Hom.: 402 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00426 AC: 5085 AN: 1192982 Hom.: 290 AF XY: 0.00358 AC XY: 2148 AN XY: 599994

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0000836

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000260

Gnomad4 FIN exome AF: 0.0000272

Gnomad4 NFE exome AF: 0.000399

Gnomad4 OTH exome AF: 0.00958

GnomAD4 genome AF: 0.0392 AC: 5971 AN: 152226 Hom.: 401 Cov.: 33 AF XY: 0.0381 AC XY: 2833 AN XY: 74420

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0337 Hom.: 31

Bravo AF: 0.0449

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	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: rs73662424; hg19: chr9-135939670;