chr16-66935658-C-A

Variant names:

• chr16-66935658-C-A
• rs764620476
• NM_001365405.1:c.23C>A

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.23C>A​(p.Ala8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,926 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CES2 NM_001365405.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.56
• Publications: 1 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=0.09538251).

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.23C>A	p.Ala8Glu	missense	Exon 1 of 12	NP_001352334.1	O00748-1
	CES2	NM_003869.6		c.23C>A	p.Ala8Glu	missense	Exon 1 of 12	NP_003860.3
	CES2	NM_198061.3		c.23C>A	p.Ala8Glu	missense	Exon 1 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.23C>A	p.Ala8Glu	missense	Exon 1 of 12	ENSP00000317842.5	O00748-1
	CES2	ENST00000417689.6	TSL:1	c.23C>A	p.Ala8Glu	missense	Exon 1 of 12	ENSP00000394452.2	O00748-2
	CES2	ENST00000971765.1		c.23C>A	p.Ala8Glu	missense	Exon 1 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450926 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722250

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.099
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.18
DANN	Benign	0.97
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.085	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.32
Sift	Benign	0.11	T
Sift4G	Uncertain	0.021	D
Vest4		0.17
MVP		0.081
MPC		0.24
ClinPred		0.13	T
GERP RS		-4.3
PromoterAI		0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs764620476; hg19: chr16-66969561;