16-66965467-A-G

Position:

• chr16-66965467-A-G

Variant summary

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

The NM_024922.6(CES3):​c.819+740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,062 control chromosomes in the GnomAD database, including 11,512 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 0.32 (11512 hom., cov: 32)
• Consequence: CES3 NM_024922.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

CES3 (HGNC:1865): (carboxylesterase 3) 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 gene is expressed in several tissues, particularly in colon, trachea and in brain, and the protein participates in colon and neural drug metabolism. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported, but the biological validity and/or full-length nature of some variants have not been determined.[provided by RefSeq, Jun 2010]

CES3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CES3	NM_024922.6	c.819+740A>G		intron_variant		ENST00000303334.9	NP_079198.2
CES3	NM_001185177.2	c.819+740A>G		intron_variant			NP_001172106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CES3	ENST00000303334.9	c.819+740A>G		intron_variant		1	NM_024922.6	ENSP00000304782.4
CES3	ENST00000394037.5	c.819+740A>G		intron_variant		1		ENSP00000377602.1
CES3	ENST00000564715.1	n.183+740A>G		intron_variant		3
CES3	ENST00000570236.1	n.819+740A>G		intron_variant		5		ENSP00000457547.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48997 AN: 151944 Hom.: 11461 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.323 AC: 49107 AN: 152062 Hom.: 11512 Cov.: 32 AF XY: 0.319 AC XY: 23750 AN XY: 74362

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.287

Alfa AF: 0.187 Hom.: 4266

Bravo AF: 0.347

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.77

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: rs13336470; hg19: chr16-66999370;