rs12149366

Positions:

• chr16-55833022-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000360526.8(CES1):​c.34T>G​(p.Ser12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,398,326 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (273 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (1061 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 ENST00000360526.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.62

Genes affected

CES1 (HGNC:1863): (carboxylesterase 1) 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. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003278941).
• BS2: High Homozygotes in GnomAdExome4 at 1061 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2	c.34T>G	p.Ser12Ala	missense_variant	1/14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.34T>G	p.Ser12Ala	missense_variant	1/14		NP_001020365.1
CES1	NM_001266.5	c.34T>G	p.Ser12Ala	missense_variant	1/14		NP_001257.4
CES1	XM_005255774.3	c.34T>G	p.Ser12Ala	missense_variant	1/14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.34T>G	p.Ser12Ala	missense_variant	1/14	1	NM_001025195.2	ENSP00000353720	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4664 AN: 124722 Hom.: 273 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00463

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0318

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0386

GnomAD3 exomes AF: 0.00649 AC: 1573 AN: 242522 Hom.: 650 AF XY: 0.00680 AC XY: 891 AN XY: 131028

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.00194

Gnomad EAS exome AF: 0.0167

Gnomad SAS exome AF: 0.0157

Gnomad FIN exome AF: 0.000524

Gnomad NFE exome AF: 0.00365

Gnomad OTH exome AF: 0.00646

GnomAD4 exome AF: 0.00232 AC: 3251 AN: 1398326 Hom.: 1061 Cov.: 32 AF XY: 0.00281 AC XY: 1953 AN XY: 695638

Gnomad4 AFR exome AF: 0.00892

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.000915

Gnomad4 EAS exome AF: 0.00413

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.00541

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0374 AC: 4665 AN: 124838 Hom.: 273 Cov.: 31 AF XY: 0.0365 AC XY: 2225 AN XY: 60886

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0318

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.0474

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0309 Hom.: 232

ESP6500AA AF: 0.00809 AC: 35

ESP6500EA AF: 0.00191 AC: 16

ExAC AF: 0.00273 AC: 322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0010
DANN	Benign	0.33
DEOGEN2	Benign	0.062	.;.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.037	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.42	N;N;N
REVEL	Benign	0.061
Sift	Benign	0.95	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.030
MVP		0.21
MPC		0.025
ClinPred		0.0041	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs12149366; hg19: chr16-55866934; COSMIC: COSV62087203; COSMIC: COSV62087203;