16-55833076-C-G

Variant names:

• chr16-55833076-C-G
• rs12149322
• NM_001025195.2:c.-21G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025195.2(CES1):​c.-21G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.13 (1374 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (2530 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-21G>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-21G>C		5_prime_UTR_variant	Exon 1 of 14		NP_001020365.1
CES1	NM_001266.5	c.-21G>C		5_prime_UTR_variant	Exon 1 of 14		NP_001257.4
CES1	XM_005255774.3	c.-21G>C		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.-21G>C		5_prime_UTR_variant	Exon 1 of 14	1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 16134 AN: 121058 Hom.: 1376 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0425

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.0116 AC: 2614 AN: 225748 AF XY: 0.0115

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00628

Gnomad ASJ exome AF: 0.00349

Gnomad EAS exome AF: 0.0370

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00806

Gnomad OTH exome AF: 0.0127

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00559 AC: 7540 AN: 1348174 Hom.: 2530 Cov.: 31 AF XY: 0.00617 AC XY: 4139 AN XY: 671272

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

African (AFR) AF: 0.00814 AC: 252 AN: 30958

American (AMR) AF: 0.00507 AC: 217 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.00465 AC: 112 AN: 24068

East Asian (EAS) AF: 0.0183 AC: 607 AN: 33084

South Asian (SAS) AF: 0.0191 AC: 1530 AN: 79918

European-Finnish (FIN) AF: 0.0108 AC: 513 AN: 47582

Middle Eastern (MID) AF: 0.0104 AC: 52 AN: 4998

European-Non Finnish (NFE) AF: 0.00373 AC: 3841 AN: 1029710

Other (OTH) AF: 0.00756 AC: 416 AN: 55024

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.133 AC: 16138 AN: 121158 Hom.: 1374 Cov.: 31 AF XY: 0.132 AC XY: 7749 AN XY: 58906

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

African (AFR) AF: 0.114 AC: 3922 AN: 34326

American (AMR) AF: 0.117 AC: 1388 AN: 11844

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 331 AN: 2832

East Asian (EAS) AF: 0.228 AC: 809 AN: 3542

South Asian (SAS) AF: 0.151 AC: 542 AN: 3598

European-Finnish (FIN) AF: 0.141 AC: 1199 AN: 8512

Middle Eastern (MID) AF: 0.209 AC: 41 AN: 196

European-Non Finnish (NFE) AF: 0.142 AC: 7632 AN: 53926

Other (OTH) AF: 0.146 AC: 244 AN: 1676

⚠️ 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: 0.0671 Hom.: 147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.46
DANN	Benign	0.56
PhyloP100		-2.3
PromoterAI		-0.24	Neutral
Mutation Taster		=300/0	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: rs12149322; hg19: chr16-55866988; COSMIC: COSV62086405; COSMIC: COSV62086405;