chr16-66940249-C-T

Variant names:

• chr16-66940249-C-T
• rs948763121
• NM_001365405.1:c.451C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365405.1(CES2):​c.451C>T​(p.Leu151Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,543,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CES2 NM_001365405.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.190
• Publications: 0 publications found

Genes affected

CES2 (HGNC:1864): (carboxylesterase 2) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08418545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365405.1. 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
	CES2	NM_001365405.1	MANE Select	c.451C>T	p.Leu151Phe	missense	Exon 4 of 12	NP_001352334.1	O00748-1
	CES2	NM_003869.6		c.451C>T	p.Leu151Phe	missense	Exon 4 of 12	NP_003860.3
	CES2	NM_198061.3		c.451C>T	p.Leu151Phe	missense	Exon 4 of 12	NP_932327.2	O00748-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES2	ENST00000317091.10	TSL:1 MANE Select	c.451C>T	p.Leu151Phe	missense	Exon 4 of 12	ENSP00000317842.5	O00748-1
	CES2	ENST00000417689.6	TSL:1	c.451C>T	p.Leu151Phe	missense	Exon 4 of 12	ENSP00000394452.2	O00748-2
	CES2	ENST00000971765.1		c.745C>T	p.Leu249Phe	missense	Exon 4 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes AF: 0.0000246 AC: 3 AN: 121822 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000543

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 248306 AF XY: 0.0000522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 22 AN: 1421914 Hom.: 0 Cov.: 32 AF XY: 0.0000198 AC XY: 14 AN XY: 705998

African (AFR) AF: 0.00 AC: 0 AN: 31910

American (AMR) AF: 0.00 AC: 0 AN: 42466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37710

South Asian (SAS) AF: 0.00 AC: 0 AN: 78736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.0000193 AC: 21 AN: 1090086

Other (OTH) AF: 0.0000171 AC: 1 AN: 58496

GnomAD4 genome AF: 0.0000246 AC: 3 AN: 121822 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 59972

African (AFR) AF: 0.00 AC: 0 AN: 32162

American (AMR) AF: 0.00 AC: 0 AN: 12032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2818

East Asian (EAS) AF: 0.00 AC: 0 AN: 4106

South Asian (SAS) AF: 0.00 AC: 0 AN: 3782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.0000543 AC: 3 AN: 55242

Other (OTH) AF: 0.00 AC: 0 AN: 1650

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.7
DANN	Benign	0.94
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.19
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.084
Sift	Benign	0.21	T
Sift4G	Benign	0.28	T
Vest4		0.21
MVP		0.040
MPC		0.32
ClinPred		0.18	T
GERP RS		-2.5
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs948763121; hg19: chr16-66974152;