rs3815583

Variant names:

• chr16-55833130-A-C
• rs3815583
• ENST00000361503.8:c.-75T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361503.8(CES1):​c.-75T>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 0.154 in 1,238,702 control chromosomes in the GnomAD database, including 21,825 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 0.23 (3207 hom., cov: 34)
  • Exomes 𝑓: 0.14 (18618 hom.)
• Consequence: CES1 ENST00000361503.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-75T>G		upstream_gene_variant		ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-75T>G		upstream_gene_variant			NP_001020365.1
CES1	NM_001266.5	c.-75T>G		upstream_gene_variant			NP_001257.4
CES1	XM_005255774.3	c.-75T>G		upstream_gene_variant			XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.-75T>G		upstream_gene_variant		1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 33809 AN: 148356 Hom.: 3202 Cov.: 34

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.143 AC: 156360 AN: 1090234 Hom.: 18618 Cov.: 18 AF XY: 0.145 AC XY: 79911 AN XY: 550250

Gnomad4 AFR exome AF: 0.225 AC: 5782 AN: 25702

Gnomad4 AMR exome AF: 0.231 AC: 9461 AN: 40968

Gnomad4 ASJ exome AF: 0.126 AC: 2828 AN: 22516

Gnomad4 EAS exome AF: 0.417 AC: 12789 AN: 30702

Gnomad4 SAS exome AF: 0.199 AC: 13687 AN: 68830

Gnomad4 FIN exome AF: 0.128 AC: 6167 AN: 48112

Gnomad4 NFE exome AF: 0.122 AC: 97597 AN: 802088

Gnomad4 Remaining exome AF: 0.154 AC: 7200 AN: 46742

GnomAD4 genome AF: 0.228 AC: 33822 AN: 148468 Hom.: 3207 Cov.: 34 AF XY: 0.228 AC XY: 16528 AN XY: 72498

Gnomad4 AFR AF: 0.283 AC: 0.282903 AN: 0.282903

Gnomad4 AMR AF: 0.230 AC: 0.230323 AN: 0.230323

Gnomad4 ASJ AF: 0.179 AC: 0.178571 AN: 0.178571

Gnomad4 EAS AF: 0.421 AC: 0.421128 AN: 0.421128

Gnomad4 SAS AF: 0.253 AC: 0.253118 AN: 0.253118

Gnomad4 FIN AF: 0.163 AC: 0.162784 AN: 0.162784

Gnomad4 NFE AF: 0.191 AC: 0.191122 AN: 0.191122

Gnomad4 OTH AF: 0.217 AC: 0.216926 AN: 0.216926

Alfa AF: 0.218 Hom.: 280

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.032
DANN	Benign	0.23
Mutation Taster		=299/1	polymorphism (auto)

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: rs3815583; hg19: chr16-55867042; COSMIC: COSV107467885; COSMIC: COSV107467885;