rs12149373

Positions:

• chr16-55833101-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361503.8(CES1):​c.-46A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 126,536 control chromosomes in the GnomAD database, including 2,198 homozygotes. 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 0.20 (2198 hom., cov: 32)
  • Exomes 𝑓: 0.019 (4720 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 ENST00000361503.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2			upstream_gene_variant		ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2			upstream_gene_variant			NP_001020365.1
CES1	NM_001266.5			upstream_gene_variant			NP_001257.4
CES1	XM_005255774.3			upstream_gene_variant			XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8			upstream_gene_variant		1	NM_001025195.2	ENSP00000353720	P4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 25218 AN: 126442 Hom.: 2200 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.0262 AC: 5391 AN: 205956 Hom.: 1589 AF XY: 0.0242 AC XY: 2701 AN XY: 111686

Gnomad AFR exome AF: 0.0371

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.0754

Gnomad SAS exome AF: 0.0260

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0288

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0189 AC: 22064 AN: 1168146 Hom.: 4720 Cov.: 26 AF XY: 0.0204 AC XY: 11885 AN XY: 581594

Gnomad4 AFR exome AF: 0.0269

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0635

Gnomad4 SAS exome AF: 0.0378

Gnomad4 FIN exome AF: 0.0435

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.199 AC: 25222 AN: 126536 Hom.: 2198 Cov.: 32 AF XY: 0.199 AC XY: 12244 AN XY: 61584

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.213

Alfa AF: 0.169 Hom.: 375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.33

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: rs12149373; hg19: chr16-55867013; COSMIC: COSV62085674; COSMIC: COSV62085674;