16-55833057-G-C

Variant names:

• chr16-55833057-G-C
• rs12149368
• NM_001025195.2:c.-2C>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.-2C>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 0.058 (599 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (1988 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 10 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=-0.84).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 7369 AN: 125968 Hom.: 600 Cov.: 31

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0568

GnomAD2 exomes AF: 0.00903 AC: 2152 AN: 238412 AF XY: 0.00931

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.00603

Gnomad ASJ exome AF: 0.00320

Gnomad EAS exome AF: 0.0302

Gnomad FIN exome AF: 0.00340

Gnomad NFE exome AF: 0.00581

Gnomad OTH exome AF: 0.00959

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00350 AC: 4859 AN: 1390058 Hom.: 1988 Cov.: 32 AF XY: 0.00393 AC XY: 2720 AN XY: 691584

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

African (AFR) AF: 0.00615 AC: 196 AN: 31858

American (AMR) AF: 0.00409 AC: 179 AN: 43740

Ashkenazi Jewish (ASJ) AF: 0.00221 AC: 55 AN: 24866

East Asian (EAS) AF: 0.0107 AC: 383 AN: 35636

South Asian (SAS) AF: 0.0155 AC: 1279 AN: 82420

European-Finnish (FIN) AF: 0.00324 AC: 163 AN: 50372

Middle Eastern (MID) AF: 0.00655 AC: 35 AN: 5346

European-Non Finnish (NFE) AF: 0.00217 AC: 2302 AN: 1058788

Other (OTH) AF: 0.00468 AC: 267 AN: 57032

⚠️ 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: 0.0584 AC: 7368 AN: 126070 Hom.: 599 Cov.: 31 AF XY: 0.0573 AC XY: 3517 AN XY: 61326

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

African (AFR) AF: 0.0531 AC: 1836 AN: 34564

American (AMR) AF: 0.0479 AC: 619 AN: 12910

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 166 AN: 2968

East Asian (EAS) AF: 0.0793 AC: 295 AN: 3718

South Asian (SAS) AF: 0.0672 AC: 255 AN: 3792

European-Finnish (FIN) AF: 0.0626 AC: 546 AN: 8726

Middle Eastern (MID) AF: 0.0962 AC: 20 AN: 208

European-Non Finnish (NFE) AF: 0.0621 AC: 3521 AN: 56662

Other (OTH) AF: 0.0577 AC: 97 AN: 1680

⚠️ 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: 0.0428 Hom.: 247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.64
PhyloP100		-1.7
PromoterAI		0.13	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: rs12149368; hg19: chr16-55866969;