chr16-66965467-A-G

Variant names:

• chr16-66965467-A-G
• rs13336470
• NM_024922.6:c.819+740A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024922.6. 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
	CES3	NM_024922.6	MANE Select	c.819+740A>G		intron	N/A	NP_079198.2
	CES3	NM_001185177.2		c.819+740A>G		intron	N/A	NP_001172106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES3	ENST00000303334.9	TSL:1 MANE Select	c.819+740A>G		intron	N/A	ENSP00000304782.4
	CES3	ENST00000394037.5	TSL:1	c.819+740A>G		intron	N/A	ENSP00000377602.1
	CES3	ENST00000564715.1	TSL:3	n.183+740A>G		intron	N/A

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

African (AFR) AF: 0.665 AC: 27549 AN: 41442

American (AMR) AF: 0.281 AC: 4299 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5166

South Asian (SAS) AF: 0.184 AC: 888 AN: 4822

European-Finnish (FIN) AF: 0.216 AC: 2296 AN: 10606

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11062 AN: 67968

Other (OTH) AF: 0.287 AC: 605 AN: 2108

Alfa AF: 0.234 Hom.: 13247

Bravo AF: 0.347

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.77
PhyloP100		0.050
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: rs13336470; hg19: chr16-66999370;