rs12149322

chr16-55833076-C-Gchr16-55833076-C-T

Variant summary

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

The NM_001025195.2(CES1):c.-21G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1374 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (2530 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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 (BayesDel_noAF=-0.82).
• BS2: High Homozygotes in GnomAdExome at 1138 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CES1	NM_001025195.2	c.-21G>C		5_prime_UTR_variant	1/14	ENST00000360526.8
CES1	NM_001025194.2	c.-21G>C		5_prime_UTR_variant	1/14
CES1	NM_001266.5	c.-21G>C		5_prime_UTR_variant	1/14
CES1	XM_005255774.3	c.-21G>C		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CES1	ENST00000360526.8	c.-21G>C		5_prime_UTR_variant	1/14	1	NM_001025195.2	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 16134 AN: 121058 Hom.: 1376 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0425

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.0116 AC: 2614 AN: 225748 Hom.: 1138 AF XY: 0.0115 AC XY: 1412 AN XY: 122568

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00628

Gnomad ASJ exome AF: 0.00349

Gnomad EAS exome AF: 0.0370

Gnomad SAS exome AF: 0.0179

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00806

Gnomad OTH exome AF: 0.0127

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00559 AC: 7540 AN: 1348174 Hom.: 2530 Cov.: 31 AF XY: 0.00617 AC XY: 4139 AN XY: 671272

Gnomad4 AFR exome AF: 0.00814

Gnomad4 AMR exome AF: 0.00507

Gnomad4 ASJ exome AF: 0.00465

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00373

Gnomad4 OTH exome AF: 0.00756

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.133 AC: 16138 AN: 121158 Hom.: 1374 Cov.: 31 AF XY: 0.132 AC XY: 7749 AN XY: 58906

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0671 Hom.: 147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.46
Dann	Benign	0.56

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: rs12149322; hg19: chr16-55866988; COSMIC: COSV62086405; COSMIC: COSV62086405;