9-133064992-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001807.6(CEL):c.341-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,606,382 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (32 hom.)
• Consequence: CEL NM_001807.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 9-133064992-C-G is Benign according to our data. Variant chr9-133064992-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1218097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00494 (752/152298) while in subpopulation SAS AF= 0.0139 (67/4830). AF 95% confidence interval is 0.0121. There are 6 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEL	NM_001807.6	c.341-48C>G		intron_variant		ENST00000372080.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEL	ENST00000372080.8	c.341-48C>G		intron_variant		5	NM_001807.6	P1

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 743 AN: 152180 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00382 AC: 917 AN: 239960 Hom.: 15 AF XY: 0.00452 AC XY: 595 AN XY: 131738

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.000205

Gnomad EAS exome AF: 0.000566

Gnomad SAS exome AF: 0.0190

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000971

Gnomad OTH exome AF: 0.00136

GnomAD4 exome AF: 0.00193 AC: 2813 AN: 1454084 Hom.: 32 Cov.: 31 AF XY: 0.00241 AC XY: 1746 AN XY: 723412

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000516

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.00494 AC: 752 AN: 152298 Hom.: 6 Cov.: 33 AF XY: 0.00541 AC XY: 403 AN XY: 74466

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00252 Hom.: 0

Bravo AF: 0.00502

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.3
Dann	Benign	0.66

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: rs140977366; hg19: chr9-135940379;