rs12149370

Positions:

• chr16-55833075-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000360526.8(CES1):​c.-20A>G 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 0.15 (1682 hom., cov: 31)
  • Exomes 𝑓: 0.0071 (2869 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 ENST00000360526.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-20A>G		5_prime_UTR_variant	1/14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-20A>G		5_prime_UTR_variant	1/14		NP_001020365.1
CES1	NM_001266.5	c.-20A>G		5_prime_UTR_variant	1/14		NP_001257.4
CES1	XM_005255774.3	c.-20A>G		5_prime_UTR_variant	1/14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.-20A>G		5_prime_UTR_variant	1/14	1	NM_001025195.2	ENSP00000353720	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 17664 AN: 120286 Hom.: 1682 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0401

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.0157 AC: 3571 AN: 226744 Hom.: 1284 AF XY: 0.0145 AC XY: 1781 AN XY: 123152

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00349

Gnomad EAS exome AF: 0.0369

Gnomad SAS exome AF: 0.0181

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00784

Gnomad OTH exome AF: 0.0138

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00706 AC: 9535 AN: 1350566 Hom.: 2869 Cov.: 31 AF XY: 0.00741 AC XY: 4985 AN XY: 672344

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.00816

Gnomad4 ASJ exome AF: 0.00473

Gnomad4 EAS exome AF: 0.0180

Gnomad4 SAS exome AF: 0.0194

Gnomad4 FIN exome AF: 0.00982

Gnomad4 NFE exome AF: 0.00374

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.147 AC: 17666 AN: 120382 Hom.: 1682 Cov.: 31 AF XY: 0.144 AC XY: 8449 AN XY: 58526

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.148

Alfa AF: 0.101 Hom.: 294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.40

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: rs12149370; hg19: chr16-55866987; COSMIC: COSV62086398; COSMIC: COSV62086398;