16-55827882-A-G

Position:

• chr16-55827882-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360526.8(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 ENST00000360526.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2	c.260+885T>C		intron_variant		ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.257+885T>C		intron_variant			NP_001020365.1
CES1	NM_001266.5	c.257+885T>C		intron_variant			NP_001257.4
CES1	XM_005255774.3	c.260+885T>C		intron_variant			XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.260+885T>C		intron_variant		1	NM_001025195.2	ENSP00000353720	P4

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

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.567

Alfa AF: 0.630 Hom.: 15425

Bravo AF: 0.532

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.54

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: rs8192935; hg19: chr16-55861794;