chr16-66935273-C-G

Variant names:

• chr16-66935273-C-G
• rs11075646
• ENST00000417689.6:c.-363C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417689.6(CES2):​c.-363C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 674,068 control chromosomes in the GnomAD database, including 4,338 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 0.14 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.083 (2306 hom.)
• Consequence: CES2 ENST00000417689.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 21 publications found

Genes affected

CES2 (HGNC:1864): (carboxylesterase 2) 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. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES2	NM_001365405.1	c.-363C>G		upstream_gene_variant		ENST00000317091.10	NP_001352334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES2	ENST00000317091.10	c.-363C>G		upstream_gene_variant		1	NM_001365405.1	ENSP00000317842.5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20683 AN: 151940 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0826

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0835 AC: 43562 AN: 522010 Hom.: 2306 Cov.: 7 AF XY: 0.0817 AC XY: 22207 AN XY: 271656

African (AFR) AF: 0.272 AC: 3870 AN: 14224

American (AMR) AF: 0.0652 AC: 1439 AN: 22056

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1867 AN: 13626

East Asian (EAS) AF: 0.0232 AC: 760 AN: 32796

South Asian (SAS) AF: 0.0652 AC: 2649 AN: 40644

European-Finnish (FIN) AF: 0.0927 AC: 3167 AN: 34168

Middle Eastern (MID) AF: 0.0854 AC: 236 AN: 2762

European-Non Finnish (NFE) AF: 0.0804 AC: 26823 AN: 333754

Other (OTH) AF: 0.0983 AC: 2751 AN: 27980

GnomAD4 genome AF: 0.136 AC: 20720 AN: 152058 Hom.: 2032 Cov.: 32 AF XY: 0.133 AC XY: 9859 AN XY: 74342

African (AFR) AF: 0.280 AC: 11605 AN: 41396

American (AMR) AF: 0.0877 AC: 1340 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.0347 AC: 179 AN: 5164

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4820

European-Finnish (FIN) AF: 0.0833 AC: 884 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0826 AC: 5614 AN: 67996

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.114 Hom.: 185

Bravo AF: 0.141

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		-1.0
PromoterAI		-0.023	Neutral
Mutation Taster		=300/0	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: rs11075646; hg19: chr16-66969176;