rs12149359

Positions:

• chr16-55832988-T-C

Variant summary

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

The NM_001025195.2(CES1):​c.52+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,460,812 control chromosomes in the GnomAD database, including 5,612 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 0.14 (1799 hom., cov: 31)
  • Exomes 𝑓: 0.0072 (3813 hom.)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CES1	NM_001025195.2	c.52+16A>G		intron_variant		ENST00000360526.8
CES1	NM_001025194.2	c.52+16A>G		intron_variant
CES1	NM_001266.5	c.52+16A>G		intron_variant
CES1	XM_005255774.3	c.52+16A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CES1	ENST00000360526.8	c.52+16A>G		intron_variant		1	NM_001025195.2	P4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 19765 AN: 139670 Hom.: 1796 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0388

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.00722 AC: 9533 AN: 1321026 Hom.: 3813 Cov.: 31 AF XY: 0.00811 AC XY: 5334 AN XY: 657882

Gnomad4 AFR exome AF: 0.00752

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.00677

Gnomad4 EAS exome AF: 0.0212

Gnomad4 SAS exome AF: 0.0222

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.00494

Gnomad4 OTH exome AF: 0.00830

GnomAD4 genome AF: 0.141 AC: 19777 AN: 139786 Hom.: 1799 Cov.: 31 AF XY: 0.140 AC XY: 9520 AN XY: 68132

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.156

Alfa AF: 0.105 Hom.: 287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.58

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: rs12149359; hg19: chr16-55866900; COSMIC: COSV62085664; COSMIC: COSV62085664;