chr16-55827882-A-G

Variant names:

• chr16-55827882-A-G
• rs8192935
• NM_001025195.2:c.260+885T>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.260+885T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,284 control chromosomes in the GnomAD database, including 24,404 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 0.55 (24404 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 48 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 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.260+885T>C		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.257+885T>C		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.257+885T>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.260+885T>C		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.257+885T>C		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.257+885T>C		intron	N/A	ENSP00000390492.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 82827 AN: 151166 Hom.: 24399 Cov.: 34

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.564

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.548 AC: 82856 AN: 151284 Hom.: 24404 Cov.: 34 AF XY: 0.545 AC XY: 40233 AN XY: 73866

African (AFR) AF: 0.326 AC: 13477 AN: 41384

American (AMR) AF: 0.602 AC: 9132 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2189 AN: 3446

East Asian (EAS) AF: 0.264 AC: 1355 AN: 5134

South Asian (SAS) AF: 0.415 AC: 1972 AN: 4748

European-Finnish (FIN) AF: 0.690 AC: 7221 AN: 10468

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.676 AC: 45731 AN: 67630

Other (OTH) AF: 0.567 AC: 1189 AN: 2096

Alfa AF: 0.613 Hom.: 60212

Bravo AF: 0.532

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.54
PhyloP100		0.35
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: rs8192935; hg19: chr16-55861794;