chr16-55810697-G-T

Variant names:

• chr16-55810697-G-T
• rs2244613
• NM_001025195.2:c.1171-33C>A

Variant summary

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

The NM_001025195.2(CES1):​c.1171-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,591,444 control chromosomes in the GnomAD database, including 500,839 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 0.77 (45158 hom., cov: 34)
  • Exomes 𝑓: 0.79 (455681 hom.)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 95 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	NM_001025195.2	MANE Select	c.1171-33C>A		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.1168-33C>A		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.1165-33C>A		intron	N/A	NP_001257.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.1171-33C>A		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.1168-33C>A		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.1165-33C>A		intron	N/A	ENSP00000390492.2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 115961 AN: 150772 Hom.: 45117 Cov.: 34

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.752

GnomAD2 exomes AF: 0.732 AC: 182802 AN: 249766 AF XY: 0.729

Gnomad AFR exome AF: 0.758

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.805

Gnomad NFE exome AF: 0.813

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.789 AC: 1136927 AN: 1440552 Hom.: 455681 Cov.: 48 AF XY: 0.783 AC XY: 561852 AN XY: 717270

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

African (AFR) AF: 0.764 AC: 25519 AN: 33384

American (AMR) AF: 0.696 AC: 31004 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 20206 AN: 25944

East Asian (EAS) AF: 0.400 AC: 15816 AN: 39520

South Asian (SAS) AF: 0.599 AC: 51258 AN: 85610

European-Finnish (FIN) AF: 0.808 AC: 42914 AN: 53142

Middle Eastern (MID) AF: 0.706 AC: 4007 AN: 5674

European-Non Finnish (NFE) AF: 0.824 AC: 900746 AN: 1093138

Other (OTH) AF: 0.763 AC: 45457 AN: 59588

⚠️ 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 AF: 0.769 AC: 116047 AN: 150892 Hom.: 45158 Cov.: 34 AF XY: 0.763 AC XY: 56268 AN XY: 73710

African (AFR) AF: 0.755 AC: 31229 AN: 41348

American (AMR) AF: 0.762 AC: 11516 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2646 AN: 3438

East Asian (EAS) AF: 0.403 AC: 2055 AN: 5098

South Asian (SAS) AF: 0.591 AC: 2803 AN: 4742

European-Finnish (FIN) AF: 0.802 AC: 8336 AN: 10400

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55067 AN: 67462

Other (OTH) AF: 0.752 AC: 1567 AN: 2084

Alfa AF: 0.792 Hom.: 157154

Bravo AF: 0.762

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.67
PhyloP100		-1.6
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2244613; hg19: chr16-55844609; COSMIC: COSV62085645; COSMIC: COSV62085645;