16-55822805-A-G

Variant names:

• chr16-55822805-A-G
• rs4122238
• NM_001025195.2:c.539+745T>C

Variant summary

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

The NM_001025195.2(CES1):​c.539+745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 151,146 control chromosomes in the GnomAD database, including 49,884 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 0.81 (49884 hom., cov: 32)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 8 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

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.539+745T>C		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.536+745T>C		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.536+745T>C		intron	N/A	NP_001257.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.539+745T>C		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.536+745T>C		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.536+745T>C		intron	N/A	ENSP00000390492.2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 122266 AN: 151026 Hom.: 49844 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.779

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.810 AC: 122356 AN: 151146 Hom.: 49884 Cov.: 32 AF XY: 0.806 AC XY: 59432 AN XY: 73780

African (AFR) AF: 0.791 AC: 32615 AN: 41252

American (AMR) AF: 0.824 AC: 12502 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2775 AN: 3454

East Asian (EAS) AF: 0.513 AC: 2643 AN: 5150

South Asian (SAS) AF: 0.701 AC: 3336 AN: 4756

European-Finnish (FIN) AF: 0.821 AC: 8600 AN: 10472

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.848 AC: 57323 AN: 67580

Other (OTH) AF: 0.807 AC: 1697 AN: 2104

Alfa AF: 0.834 Hom.: 38838

Bravo AF: 0.804

Asia WGS AF: 0.649 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.60
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs4122238; hg19: chr16-55856717;