NM_001365405.1:c.915+70C>T

Variant names:

• chr16-66941292-C-T
• rs11568310
• NM_001365405.1:c.915+70C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001365405.1(CES2):​c.915+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,579,010 control chromosomes in the GnomAD database, including 255 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 0.014 (26 hom., cov: 33)
  • Exomes 𝑓: 0.016 (229 hom.)
• Consequence: CES2 NM_001365405.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0141 (2151/152312) while in subpopulation NFE AF= 0.0214 (1454/68018). AF 95% confidence interval is 0.0205. There are 26 homozygotes in gnomad4. There are 1041 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES2	NM_001365405.1	c.915+70C>T		intron_variant	Intron 6 of 11	ENST00000317091.10	NP_001352334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES2	ENST00000317091.10	c.915+70C>T		intron_variant	Intron 6 of 11	1	NM_001365405.1	ENSP00000317842.5

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2153 AN: 152194 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0163 AC: 23187 AN: 1426698 Hom.: 229 Cov.: 31 AF XY: 0.0161 AC XY: 11350 AN XY: 706810

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.00939

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.00294

Gnomad4 FIN exome AF: 0.0247

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0141 AC: 2151 AN: 152312 Hom.: 26 Cov.: 33 AF XY: 0.0140 AC XY: 1041 AN XY: 74480

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0182 Hom.: 16

Bravo AF: 0.0120

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11568310; hg19: chr16-66975195;