rs8192950

chr16-55808492-T-G

Variant summary

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

The NM_001025195.2(CES1):c.1318+2025A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 150,922 control chromosomes in the GnomAD database, including 21,798 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 0.51 (21798 hom., cov: 34)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

Genes affected

CES1 (HGNC:1863): (carboxylesterase 1) 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 enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CES1	NM_001025195.2	c.1318+2025A>C		intron_variant		ENST00000360526.8
CES1	NM_001025194.2	c.1315+2025A>C		intron_variant
CES1	NM_001266.5	c.1312+2025A>C		intron_variant
CES1	XM_005255774.3	c.1315+2025A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CES1	ENST00000360526.8	c.1318+2025A>C		intron_variant		1	NM_001025195.2	P4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 76904 AN: 150806 Hom.: 21794 Cov.: 34

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.510 AC: 76930 AN: 150922 Hom.: 21798 Cov.: 34 AF XY: 0.506 AC XY: 37304 AN XY: 73710

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.509

Alfa AF: 0.590 Hom.: 10195

Bravo AF: 0.493

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.2
Dann	Benign	0.53

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: rs8192950; hg19: chr16-55842404;