rs488087

Variant names:

• chr9-133071212-C-T
• rs488087
• NM_001807.6:c.1710C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133071212-C-T
• chr9-133071212-C-A
• chr9-133071212-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001807.6(CEL):​c.1710C>T​(p.Pro570Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,117,868 control chromosomes in the GnomAD database, including 25,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5582 hom., cov: 29)
  • Exomes 𝑓: 0.13 (19784 hom.)
• Consequence: CEL NM_001807.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.46
• Publications: 14 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), Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-133071212-C-T is Benign according to our data. Variant chr9-133071212-C-T is described in ClinVar as Benign. ClinVar VariationId is 128685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

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.1710C>T	p.Pro570Pro	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.1710C>T	p.Pro570Pro	synonymous	Exon 11 of 11	ENSP00000361151.6	P19835-1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 37426 AN: 147170 Hom.: 5575 Cov.: 29

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.230

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.110 AC: 17191 AN: 156926 AF XY: 0.0991

Gnomad AFR exome AF: 0.0783

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.135 AC: 130647 AN: 970590 Hom.: 19784 Cov.: 32 AF XY: 0.138 AC XY: 68357 AN XY: 495092

African (AFR) AF: 0.0706 AC: 1962 AN: 27782

American (AMR) AF: 0.161 AC: 5256 AN: 32648

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 3965 AN: 19970

East Asian (EAS) AF: 0.149 AC: 5479 AN: 36752

South Asian (SAS) AF: 0.0554 AC: 4366 AN: 78748

European-Finnish (FIN) AF: 0.329 AC: 12735 AN: 38724

Middle Eastern (MID) AF: 0.176 AC: 868 AN: 4922

European-Non Finnish (NFE) AF: 0.129 AC: 88696 AN: 686116

Other (OTH) AF: 0.163 AC: 7320 AN: 44928

GnomAD4 genome AF: 0.254 AC: 37459 AN: 147278 Hom.: 5582 Cov.: 29 AF XY: 0.255 AC XY: 18363 AN XY: 71874

African (AFR) AF: 0.151 AC: 6069 AN: 40292

American (AMR) AF: 0.271 AC: 4058 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1027 AN: 3412

East Asian (EAS) AF: 0.183 AC: 887 AN: 4854

South Asian (SAS) AF: 0.0936 AC: 434 AN: 4638

European-Finnish (FIN) AF: 0.381 AC: 3890 AN: 10220

Middle Eastern (MID) AF: 0.227 AC: 63 AN: 278

European-Non Finnish (NFE) AF: 0.306 AC: 20121 AN: 65692

Other (OTH) AF: 0.269 AC: 545 AN: 2026

Alfa AF: 0.226 Hom.: 880

Bravo AF: 0.247

Asia WGS AF: 0.100 AC: 334 AN: 3314

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.14
DANN	Benign	0.74
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs488087; hg19: chr9-135946599; COSMIC: COSV60829876;