16-55808492-T-G

Variant names:

• chr16-55808492-T-G
• rs8192950
• NM_001025195.2:c.1318+2025A>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.1318+2025A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 150,922 control chromosomes in the GnomAD database, including 21,798 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 0.51 (21798 hom., cov: 34)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 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.1318+2025A>C		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.1315+2025A>C		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.1312+2025A>C		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.1318+2025A>C		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.1315+2025A>C		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.1312+2025A>C		intron	N/A	ENSP00000390492.2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 76904 AN: 150806 Hom.: 21794 Cov.: 34

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.510 AC: 76930 AN: 150922 Hom.: 21798 Cov.: 34 AF XY: 0.506 AC XY: 37304 AN XY: 73710

African (AFR) AF: 0.275 AC: 11317 AN: 41112

American (AMR) AF: 0.576 AC: 8727 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1934 AN: 3456

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5160

South Asian (SAS) AF: 0.344 AC: 1640 AN: 4764

European-Finnish (FIN) AF: 0.682 AC: 7115 AN: 10440

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43530 AN: 67560

Other (OTH) AF: 0.509 AC: 1058 AN: 2080

Alfa AF: 0.569 Hom.: 14928

Bravo AF: 0.493

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.53
PhyloP100		0.78
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: rs8192950; hg19: chr16-55842404;