16-55832375-A-G

Variant names:

• chr16-55832375-A-G
• rs7188256
• NM_001025195.2:c.52+629T>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.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 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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.52+629T>C		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.52+629T>C		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.52+629T>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.52+629T>C		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.52+629T>C		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.52+629T>C		intron	N/A	ENSP00000390492.2

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

African (AFR) AF: 0.123 AC: 4771 AN: 38812

American (AMR) AF: 0.0441 AC: 655 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.0563 AC: 188 AN: 3342

East Asian (EAS) AF: 0.0108 AC: 55 AN: 5088

South Asian (SAS) AF: 0.0893 AC: 417 AN: 4668

European-Finnish (FIN) AF: 0.0579 AC: 587 AN: 10132

Middle Eastern (MID) AF: 0.102 AC: 28 AN: 274

European-Non Finnish (NFE) AF: 0.0433 AC: 2884 AN: 66652

Other (OTH) AF: 0.0670 AC: 135 AN: 2016

Alfa AF: 0.0206 Hom.: 11

Bravo AF: 0.0661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.53
PhyloP100		-0.28
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: rs7188256; hg19: chr16-55866287;