rs12149370

Variant names:

• chr16-55833075-T-C
• rs12149370
• NM_001025195.2:c.-20A>G

Variant summary

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

The NM_001025195.2(CES1):​c.-20A>G 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 0.15 (1682 hom., cov: 31)
  • Exomes 𝑓: 0.0071 (2869 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 6 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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	NM_001025195.2	MANE Select	c.-20A>G		5_prime_UTR	Exon 1 of 14	NP_001020366.1	P23141-2
	CES1	NM_001025194.2		c.-20A>G		5_prime_UTR	Exon 1 of 14	NP_001020365.1	P23141-1
	CES1	NM_001266.5		c.-20A>G		5_prime_UTR	Exon 1 of 14	NP_001257.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.-20A>G		5_prime_UTR	Exon 1 of 14	ENSP00000353720.4	P23141-2
	CES1	ENST00000361503.8	TSL:1	c.-20A>G		5_prime_UTR	Exon 1 of 14	ENSP00000355193.4	P23141-1
	CES1	ENST00000422046.6	TSL:1	c.-20A>G		5_prime_UTR	Exon 1 of 14	ENSP00000390492.2	P23141-3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 17664 AN: 120286 Hom.: 1682 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0401

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.0157 AC: 3571 AN: 226744 AF XY: 0.0145

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00349

Gnomad EAS exome AF: 0.0369

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00784

Gnomad OTH exome AF: 0.0138

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00706 AC: 9535 AN: 1350566 Hom.: 2869 Cov.: 31 AF XY: 0.00741 AC XY: 4985 AN XY: 672344

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

African (AFR) AF: 0.0615 AC: 1911 AN: 31082

American (AMR) AF: 0.00816 AC: 350 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.00473 AC: 114 AN: 24102

East Asian (EAS) AF: 0.0180 AC: 597 AN: 33208

South Asian (SAS) AF: 0.0194 AC: 1554 AN: 80110

European-Finnish (FIN) AF: 0.00982 AC: 467 AN: 47580

Middle Eastern (MID) AF: 0.0150 AC: 75 AN: 5016

European-Non Finnish (NFE) AF: 0.00374 AC: 3854 AN: 1031508

Other (OTH) AF: 0.0111 AC: 613 AN: 55090

⚠️ 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: 0.147 AC: 17666 AN: 120382 Hom.: 1682 Cov.: 31 AF XY: 0.144 AC XY: 8449 AN XY: 58526

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

African (AFR) AF: 0.167 AC: 5743 AN: 34412

American (AMR) AF: 0.120 AC: 1417 AN: 11768

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 321 AN: 2810

East Asian (EAS) AF: 0.220 AC: 767 AN: 3486

South Asian (SAS) AF: 0.145 AC: 521 AN: 3582

European-Finnish (FIN) AF: 0.137 AC: 1159 AN: 8458

Middle Eastern (MID) AF: 0.205 AC: 39 AN: 190

European-Non Finnish (NFE) AF: 0.139 AC: 7426 AN: 53328

Other (OTH) AF: 0.148 AC: 245 AN: 1650

⚠️ 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: 0.101 Hom.: 294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-3.0
PromoterAI		0.031	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12149370;

hg19: chr16-55866987;

COSMIC: COSV62086398;

COSMIC: COSV62086398;