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
• Publications: 29 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361503.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	NM_001025195.2	MANE Select	c.-75T>G		upstream_gene	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.-75T>G		upstream_gene	N/A	NP_001020365.1
	CES1	NM_001266.5		c.-75T>G		upstream_gene	N/A	NP_001257.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000361503.8	TSL:1	c.-75T>G		5_prime_UTR	Exon 1 of 14	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.-75T>G		5_prime_UTR	Exon 1 of 14	ENSP00000390492.2
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.-75T>G		upstream_gene	N/A	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

African (AFR) AF: 0.225 AC: 5782 AN: 25702

American (AMR) AF: 0.231 AC: 9461 AN: 40968

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 2828 AN: 22516

East Asian (EAS) AF: 0.417 AC: 12789 AN: 30702

South Asian (SAS) AF: 0.199 AC: 13687 AN: 68830

European-Finnish (FIN) AF: 0.128 AC: 6167 AN: 48112

Middle Eastern (MID) AF: 0.186 AC: 849 AN: 4574

European-Non Finnish (NFE) AF: 0.122 AC: 97597 AN: 802088

Other (OTH) 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

African (AFR) AF: 0.283 AC: 11530 AN: 40756

American (AMR) AF: 0.230 AC: 3453 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 610 AN: 3416

East Asian (EAS) AF: 0.421 AC: 2061 AN: 4894

South Asian (SAS) AF: 0.253 AC: 1177 AN: 4650

European-Finnish (FIN) AF: 0.163 AC: 1677 AN: 10302

Middle Eastern (MID) AF: 0.225 AC: 62 AN: 276

European-Non Finnish (NFE) AF: 0.191 AC: 12658 AN: 66230

Other (OTH) AF: 0.217 AC: 446 AN: 2056

Alfa AF: 0.218 Hom.: 280

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.032
DANN	Benign	0.23
PhyloP100		-3.1
PromoterAI		0.073	Neutral
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

Other links and lift over

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