rs77696629

Variant names:

• chr9-133070628-T-A
• NM_001807.6:c.1454T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133070628-T-A
• chr9-133070628-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001807.6(CEL):​c.1454T>A​(p.Ile485Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I485T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEL NM_001807.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEL	NM_001807.6	c.1454T>A	p.Ile485Asn	missense_variant	Exon 10 of 11	ENST00000372080.8	NP_001798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEL	ENST00000372080.8	c.1454T>A	p.Ile485Asn	missense_variant	Exon 10 of 11	5	NM_001807.6	ENSP00000361151.6

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398266 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 694112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.35e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.22	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.91
MVP		0.94
MPC		1.2
ClinPred		1.0	D
GERP RS		4.6
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135946015;