16-55833094-T-C

Variant names:

• chr16-55833094-T-C
• rs12149371
• NM_001025195.2:c.-39A>G

Variant summary

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

The NM_001025195.2(CES1):​c.-39A>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 0.0547 in 1,359,412 control chromosomes in the GnomAD database, including 12,347 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 0.24 (3782 hom., cov: 32)
  • Exomes 𝑓: 0.035 (8565 hom.)
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.59
• Publications: 9 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=-1.03).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-39A>G		5_prime_UTR_variant	Exon 1 of 14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-39A>G		5_prime_UTR_variant	Exon 1 of 14		NP_001020365.1
CES1	NM_001266.5	c.-39A>G		5_prime_UTR_variant	Exon 1 of 14		NP_001257.4
CES1	XM_005255774.3	c.-39A>G		5_prime_UTR_variant	Exon 1 of 14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.-39A>G		5_prime_UTR_variant	Exon 1 of 14	1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 30760 AN: 125826 Hom.: 3778 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.248

GnomAD2 exomes AF: 0.0484 AC: 10381 AN: 214430 AF XY: 0.0440

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.0297

Gnomad ASJ exome AF: 0.0591

Gnomad EAS exome AF: 0.0671

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0499

GnomAD4 exome AF: 0.0354 AC: 43609 AN: 1233492 Hom.: 8565 Cov.: 29 AF XY: 0.0360 AC XY: 22065 AN XY: 613338

African (AFR) AF: 0.189 AC: 5526 AN: 29282

American (AMR) AF: 0.0335 AC: 1355 AN: 40466

Ashkenazi Jewish (ASJ) AF: 0.0636 AC: 1452 AN: 22816

East Asian (EAS) AF: 0.0516 AC: 1492 AN: 28888

South Asian (SAS) AF: 0.0413 AC: 2962 AN: 71642

European-Finnish (FIN) AF: 0.0367 AC: 1577 AN: 43008

Middle Eastern (MID) AF: 0.124 AC: 559 AN: 4492

European-Non Finnish (NFE) AF: 0.0276 AC: 25983 AN: 942224

Other (OTH) AF: 0.0533 AC: 2703 AN: 50674

GnomAD4 genome AF: 0.244 AC: 30781 AN: 125920 Hom.: 3782 Cov.: 32 AF XY: 0.241 AC XY: 14750 AN XY: 61134

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.317 AC: 11662 AN: 36822

American (AMR) AF: 0.209 AC: 2514 AN: 12054

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 597 AN: 2902

East Asian (EAS) AF: 0.324 AC: 1217 AN: 3758

South Asian (SAS) AF: 0.221 AC: 836 AN: 3778

European-Finnish (FIN) AF: 0.183 AC: 1587 AN: 8694

Middle Eastern (MID) AF: 0.368 AC: 86 AN: 234

European-Non Finnish (NFE) AF: 0.212 AC: 11729 AN: 55242

Other (OTH) AF: 0.252 AC: 445 AN: 1768

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.103 Hom.: 252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.011
DANN	Benign	0.23
PhyloP100		-4.6
PromoterAI		-0.032	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: rs12149371; hg19: chr16-55867006; COSMIC: COSV62085668; COSMIC: COSV62085668;