rs551163563

Variant names:

• chr9-133064377-CT-C
• rs551163563
• NM_001807.6:c.67-26delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001807.6(CEL):​c.67-26delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,612,712 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: CEL NM_001807.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.202
• Publications: 1 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: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-133064377-CT-C is Benign according to our data. Variant chr9-133064377-CT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1186605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00607 (924/152318) while in subpopulation AFR AF = 0.0212 (881/41570). AF 95% confidence interval is 0.02. There are 13 homozygotes in GnomAd4. There are 440 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 924 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	NM_001807.6	MANE Select	c.67-26delT		intron	N/A	NP_001798.3	P19835-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEL	ENST00000372080.8	TSL:5 MANE Select	c.67-26delT		intron	N/A	ENSP00000361151.6	P19835-1

Frequencies

GnomAD3 genomes AF: 0.00606 AC: 922 AN: 152198 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00164 AC: 406 AN: 247386 AF XY: 0.00112

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.000957

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000620 AC: 905 AN: 1460394 Hom.: 10 Cov.: 32 AF XY: 0.000486 AC XY: 353 AN XY: 726558

African (AFR) AF: 0.0225 AC: 754 AN: 33478

American (AMR) AF: 0.00107 AC: 48 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52250

Middle Eastern (MID) AF: 0.000715 AC: 4 AN: 5596

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111948

Other (OTH) AF: 0.00118 AC: 71 AN: 60350

GnomAD4 genome AF: 0.00607 AC: 924 AN: 152318 Hom.: 13 Cov.: 33 AF XY: 0.00591 AC XY: 440 AN XY: 74484

African (AFR) AF: 0.0212 AC: 881 AN: 41570

American (AMR) AF: 0.00189 AC: 29 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.000304 Hom.: 0

Bravo AF: 0.00711

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs551163563; hg19: chr9-135939764;