rs587780307

Variant names:

• chr9-133071434-G-C
• rs587780307
• NM_001807.6:c.1932G>C
• CEL p.Gly644Gly

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001807.6(CEL):​c.1932G>C​(p.Gly644Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEL NM_001807.6 synonymous
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.60
• 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: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, Genomics England PanelApp
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.

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.1932G>C	p.Gly644Gly	synonymous	Exon 11 of 11	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.1932G>C	p.Gly644Gly	synonymous	Exon 11 of 11	ENSP00000361151.6	P19835-1

Frequencies

GnomAD3 genomes AF: 0.0000353 AC: 1 AN: 28360 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000186 AC: 1 AN: 53760 Hom.: 0 Cov.: 0 AF XY: 0.0000341 AC XY: 1 AN XY: 29304

African (AFR) AF: 0.00 AC: 0 AN: 984

American (AMR) AF: 0.00 AC: 0 AN: 1142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3716

South Asian (SAS) AF: 0.000246 AC: 1 AN: 4060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34040

Other (OTH) AF: 0.00 AC: 0 AN: 2964

GnomAD4 genome AF: 0.0000353 AC: 1 AN: 28360 Hom.: 0 Cov.: 5 AF XY: 0.0000735 AC XY: 1 AN XY: 13608

African (AFR) AF: 0.00 AC: 0 AN: 6640

American (AMR) AF: 0.00 AC: 0 AN: 3342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 810

East Asian (EAS) AF: 0.000769 AC: 1 AN: 1300

South Asian (SAS) AF: 0.00 AC: 0 AN: 812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 46

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14022

Other (OTH) AF: 0.00 AC: 0 AN: 362

Alfa AF: 0.00194 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587780307;

hg19: chr9-135946821;

COSMIC: COSV60829033;