16-55833057-G-C

Position:

• chr16-55833057-G-C

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-2C>G		5_prime_UTR_variant	1/14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-2C>G		5_prime_UTR_variant	1/14		NP_001020365.1
CES1	NM_001266.5	c.-2C>G		5_prime_UTR_variant	1/14		NP_001257.4
CES1	XM_005255774.3	c.-2C>G		5_prime_UTR_variant	1/14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.-2C>G		5_prime_UTR_variant	1/14	1	NM_001025195.2	ENSP00000353720	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 7369 AN: 125968 Hom.: 600 Cov.: 31 FAILED QC

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

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

Gnomad4 AFR exome AF: 0.00615

Gnomad4 AMR exome AF: 0.00409

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.0155

Gnomad4 FIN exome AF: 0.00324

Gnomad4 NFE exome AF: 0.00217

Gnomad4 OTH exome AF: 0.00468

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

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.0793

Gnomad4 SAS AF: 0.0672

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0428 Hom.: 247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs12149368; hg19: chr16-55866969;