rs11075646

Positions:

• chr16-66935273-C-G

Variant summary

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

The ENST00000417689.6(CES2):​c.-363C>G variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CES2	NM_003869.6	c.-363C>G		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CES2	ENST00000417689.6	c.-363C>G		5_prime_UTR_variant	1/12	1
CES2	ENST00000561697.5	c.-85+360C>G		intron_variant		3
CES2	ENST00000566182.1	n.656C>G		non_coding_transcript_exon_variant	2/2	3
CES2	ENST00000568470.6	c.-363C>G		5_prime_UTR_variant, NMD_transcript_variant	1/12	2

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

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.0652

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0232

Gnomad4 SAS exome AF: 0.0652

Gnomad4 FIN exome AF: 0.0927

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0983

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

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0833

Gnomad4 NFE AF: 0.0826

Gnomad4 OTH AF: 0.125

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

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: rs11075646; hg19: chr16-66969176;