chr16-55832375-A-G

Position:

• chr16-55832375-A-G

Variant summary

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

The ENST00000360526.8(CES1):​c.52+629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 146,722 control chromosomes in the GnomAD database, including 329 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 0.067 (329 hom., cov: 33)
• Consequence: CES1 ENST00000360526.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES1	NM_001025195.2	c.52+629T>C		intron_variant		ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.52+629T>C		intron_variant			NP_001020365.1
CES1	NM_001266.5	c.52+629T>C		intron_variant			NP_001257.4
CES1	XM_005255774.3	c.52+629T>C		intron_variant			XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.52+629T>C		intron_variant		1	NM_001025195.2	ENSP00000353720	P4

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 9779 AN: 146614 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0563

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.0993

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0682

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

GnomAD4 genome AF: 0.0667 AC: 9785 AN: 146722 Hom.: 329 Cov.: 33 AF XY: 0.0670 AC XY: 4805 AN XY: 71748

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0563

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0206 Hom.: 11

Bravo AF: 0.0661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.53

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: rs7188256; hg19: chr16-55866287;