chr16-66940239-C-T

Variant names:

• chr16-66940239-C-T
• rs150573301
• NM_001365405.1:c.441C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001365405.1(CES2):​c.441C>T​(p.His147His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,538,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: CES2 NM_001365405.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-66940239-C-T is Benign according to our data. Variant chr16-66940239-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2646608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.

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.441C>T	p.His147His	synonymous	Exon 4 of 12	NP_001352334.1	O00748-1
	CES2	NM_003869.6		c.441C>T	p.His147His	synonymous	Exon 4 of 12	NP_003860.3
	CES2	NM_198061.3		c.441C>T	p.His147His	synonymous	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.441C>T	p.His147His	synonymous	Exon 4 of 12	ENSP00000317842.5	O00748-1
	CES2	ENST00000417689.6	TSL:1	c.441C>T	p.His147His	synonymous	Exon 4 of 12	ENSP00000394452.2	O00748-2
	CES2	ENST00000971765.1		c.735C>T	p.His245His	synonymous	Exon 4 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes AF: 0.000123 AC: 16 AN: 130030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000304

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: 0.000153

Gnomad OTH AF: 0.00112

GnomAD2 exomes AF: 0.0000759 AC: 19 AN: 250426 AF XY: 0.0000812

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000143 AC: 201 AN: 1408854 Hom.: 1 Cov.: 32 AF XY: 0.000136 AC XY: 95 AN XY: 699218

African (AFR) AF: 0.00 AC: 0 AN: 31288

American (AMR) AF: 0.000265 AC: 11 AN: 41432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24832

East Asian (EAS) AF: 0.00 AC: 0 AN: 36682

South Asian (SAS) AF: 0.00 AC: 0 AN: 76524

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.000169 AC: 183 AN: 1083360

Other (OTH) AF: 0.000104 AC: 6 AN: 57826

GnomAD4 genome AF: 0.000123 AC: 16 AN: 130144 Hom.: 0 Cov.: 32 AF XY: 0.0000783 AC XY: 5 AN XY: 63820

African (AFR) AF: 0.0000289 AC: 1 AN: 34648

American (AMR) AF: 0.000304 AC: 4 AN: 13174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3042

East Asian (EAS) AF: 0.00 AC: 0 AN: 4202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 220

European-Non Finnish (NFE) AF: 0.000153 AC: 9 AN: 58950

Other (OTH) AF: 0.00111 AC: 2 AN: 1802

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.000132

EpiCase AF: 0.000219

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.16
DANN	Benign	0.80
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs150573301; hg19: chr16-66974142; COSMIC: COSV57697280; COSMIC: COSV57697280;